You are on page 1of 24

CHAPTER 1

Emotions and
the Aging Brain
Regrets and Remedies

Jaak Panksepp ~nd Anesa Miller


Department of Psychology Memorial Foundation for Lost Children
Bowling Green State University Bowling Green, Ohio
Bowling Green, Ohio

I. I N T R O D U C T I O N

Although there is now a b u n d a n t evidence that a variety of e m o t i o n a l


systems have their basis in the shared heritage of the old m a m m a l i a n (lim-
bic) brain, quite similar in rats, cats, monkeys, and humans, there is virtu-
ally no evidence of how these systems age across the life span of organisms.
Much m o r e is known a b o u t the early d e v e l o p m e n t of these systems. This
leaves researchers in the creative position of surmising rather than sum-
marizing scholarly accomplishments in the area. Some information that is
e m e r g i n g from the study of early developmental phases (Panksepp, Knut-
son, & Pruitt, in press) allows one to anticipate what may be f o u n d when
psychobiologists eventually focus their empirical tools on the question
of how e m o t i o n a l matters change as the brain enters old age. What we can
provide here is an overall perspective on the types of brain systems that
should be studied in relation to aging, and we will also share some pro-
vocative recent work on n e u r o c h e m i c a l manipulations that can p o s t p o n e
the decay of e m o t i o n a l vitality that reduces the joy of living in old age.
We will focus on the basic e m o t i o n a l systems that are organized
within subcortical circuits that are shared by all m a m m a l s (MacLean,

Handbook of Emotion, Adult Development, and Aging


Copyright 9 1996 by Academic Press, Inc. All rights of reproduction in any form reserved.
4 Jaak Panksepp and Anesa Miller

1990; Panksepp, 1982, 1985a, 1991, in press). We will use the convention
of labeling these systems by simple emotional terms, capitalized to high-
light that they do not just designate the garden-varieties of emotional
feelings, but also the neurological bases of such feelings. These include
neural circuits that mediate separation distress and sorrow (the PANIC
system), ones that mediate playfulness and joy (the PLAY system), ones
that control sexual desires and pleasures (the LUST systems), and ones
for maternal (or parental) nurturance and social b o n d i n g (the ACCEP-
TANCE system). There may be others, such as a system for social DOMI-
NANCE, but because it is debatable whether these are distinct from the
others mentioned, we will not discuss them as separate systems.
All of those listed above are based in the extended limbic areas of the
brain, as defined by MacLean (1990). In addition, there are the more
cold-blooded, reptilian emotional systems of FEAR and RAGE, as well as
the ever powerful appetitive motivational system that mediates explor-
atory drives and foraging behavior (which we have previously called the
Expectancy System but will henceforth term the SEEKING system).
Some of these, such as FEAR and RAGE, are closely intertwined and me-
diate, respectively, an organism's defense of bodily integrity and its re-
sponse to irritations that thwart freedom of action and possession of re-
sources. The extensive and compelling neural evidence on how these
psychobehavioral systems function during early development has been
extensively discussed elsewhere (Panksepp, in press). In the present
chapter we would like to summarize how their sensitivities and respon-
sivities change in old age; because we cannot do so on the basis of avail-
able empirical evidence, we shall proceed more on the basis of rational
argumentation.
One general factor that complicates any life span analysis of brain
emotional systems is that a great deal of learning transpires, and many
habits are established, broken, and otherwise changed over time. Be-
cause of these fluxes, there is really no way to analyze the changing sensi-
tivities of emotional circuits by using behavioral means alone. One must
analyze the changing dynamics of the underlying neural systems using
anatomical and electrophysiological approaches, and those analyses have
started in earnest but without parallel behavioral data, so it is difficult to
relate those findings to psychological issues.

II. E M O T I O N A L LEARNING AND THE AGING BRAIN

The brain's intrinsic emotional c o m m a n d systems serve to coordi-


nate instinctual behavioral and affective responses to archetypal survival
needs. In addition to generating subjective emotional feelings, they acti-
CHAPTER 1 Emotions and the Aging Brain 5

vate changes in behavior, physiological and h o r m o n a l balances, and they


probably prepare the way for cognitive styles of handling i m p o r t a n t situ-
ations. In addition to coordinating those peripheral effects, the affective
feelings that emotional systems generate appear to provide internal value
gauges to p r o m o t e efficient coding of external events in the interest of
future behavioral actions (Panksepp, 1991, in press). In other words, the
feelings we experience play a key role in various affect-related special-
purpose learning and cognitive systems (Barkow, Cosmides, & Tooby,
1995). This is presumably so because the brain has a m u c h easier time re-
trieving certain types of information if it can resurrect an emotional state
with which external information has been linked in memory. For in-
stance, when one is not caught up in the throes of rage, it is difficult to
outline dastardly plans of revenge in realistic detail. However, when gen-
uine anger is aroused, all the necessary strategies fill one's mind with ease.
W h e n we are young, our emotional systems help establish specific types
of behavioral and psychological habits, d e p e n d i n g on the success of these
behaviors in affecting outcomes in desirable or undesirable ways. How-
ever, once behavioral and cognitive habits become ingrained, the role of
emotional systems may recede to the b a c k g r o u n d as c o m p a r e d to their
centrality in youth.
At this point it may also be worth highlighting the Kennard Principle,
which states that young people generally recover from the same types of
brain damage more rapidly and effectively than older people (see Kolb
& Whishaw, 1990). This is especially evident following cortical damage,
for instance, to speech cortex. A massive left h e m i s p h e r e infarct does not
impair a person's language abilities in youth as m u c h as in old age. But
behavioral neuroscience has now outlined a host of opposite effectsm
anti-Kennard effectsmwhereby the consequences of damage are more se-
vere in youth. These types of damage are typically subcortically situated
in the d e e p e r recesses of the basic operating systems of the brain, such as
the emotional ones. This suggests that without adequate functions within
the operating systems, young organisms cannot develop and thrive nor-
mally, whereas older individuals, who have lifelong habits backing up
their behavioral strategies, can often cope better. For instance, young rats
given lateral hypothalamic lesions in the heart of the SEEKING system,
tend to show a p e r m a n e n t failure-to-thrive syndrome, whereas older ani-
mals can be coaxed to recover and live on their own abilities again (Almli
& Golden, 1974). Similarly, aspiration of the olfactory bulbs (i.e., bulbec-
tomy) and temporal l o b e / a m y g d a l a can compromise the survival chances
of infant rats completely, whereas older animals tolerate such p r o c e d u r e s
well. Likewise, in sexually mature animals bulbectomy does not modify
male sexuality, whereas similar damage in young animals permanently
abolishes sexual activity (Wilhelmsson & Larsson, 1973). Apparently, the
6 Jaak Panksepp and Anesa Miller

consequences of earlier learning in such brain-damaged adults help sus-


tain c o m p e t e n t behavior. W h e n the basic operating systems of the brain
have been allowed to develop to maturity, they have apparently estab-
lished behavioral subroutines that help p r o m o t e survival.
As a corollary to this, it seems that a mature organism's cognitive, be-
havioral, and emotional style has been streamlined to the point that, at
least in day-to-day circumstances, powerful emotions are activated less fre-
quently than they were in youth. Does this m e a n that e m o t i o n a l systems
have deteriorated at the physiological level, or does it simply indicate that
behavioral habits tend to shape our lives so that emotional arousal is no
longer as necessary as it once was for guiding our motivations? One way to
describe the situation is to suppose that over a person's lifetime, the expe-
rience and expression of various emotions gradually creates a relatively in-
tangible neurodynamic structure composed of individual habits and social
responses. The quality of an elderly person's emotional life d e p e n d s on
the successful maintenance of these habits and the reactions they elicit.
Considered in this way, an older person's internally e x p e r i e n c e d emo-
tions may be more diffused than they were in youth, but at the same time,
they may b e c o m e socially more powerful. For example, in an ideal sce-
nario, over the course of a lifetime devoted to caring for her family, a
m o t h e r establishes behavioral patterns that express love and nurturance,
which in turn p r o d u c e loving responses. Although the woman's intense
feeling of attachment to her babies inevitably u n d e r g o e s modifications
as the children grow and achieve i n d e p e n d e n c e , if her pattern of care-
giving is successful, then her love becomes established as a social fact, re-
placing individual intensity with a b r o a d e r kind of strength that relies on
a network of participants.
Similarly, a young person's experience of rage may be intense and
even destructive, but ultimately, the same e m o t i o n can lead to b r o a d e r
and m o r e powerful results (whether for good or ill) if it is built, over time,
into a social m o v e m e n t to counteract the thwarting factors that aroused
the rage to begin with. Sadly, neurobehavioral data can tell us little, thus
far, about the mechanisms of aging in relation to such changes in emo-
tional experience. Still, as one step toward a greater understanding, we
will discuss each of the major e m o t i o n a l systems from a perspective that
may prove useful for future inquiry.

III. T H E BASIC E M O T I O N A L SYSTEMS

A. The Separation Distress~PANIC System


It seems logical that certain emotional experiences are crucial to the
p r o p e r d e v e l o p m e n t of young organisms and, therefore, tend to be m o r e
CHAPTER 1 Emotions and the Aging Brain 7

acute at an early age than they will b e c o m e later in life. The PANIC sys-
tem affords a good example, because cross-species c o m p a r i s o n shows that
activity in this system can vary as a function of the organism's relative n e e d
for care and protection. The n e u r o d y n a m i c s of the brain systems that gen-
erate separation calls (or distress vocalizations, DVs) vary markedly in
species d e p e n d i n g on their ecological circumstances and modes of social
bonding. For instance, herbivores that are born precocious (at a relatively
mature level of m o t o r d e v e l o p m e n t ) , such as guinea pigs, chickens, and
ducks, d e m o n s t r a t e separation distress on the first day of life and exhibit
a p r o l o n g e d inverted-U type of trajectory of separation calls that contin-
ues until p u b e r t y (Panksepp et al., in press; Pettijohn, 1979). Altricial an-
imals, such as most carnivores, including dogs, exhibit similar p r o l o n g e d
patterns of separation distress (Scott, Stewart, & DeGhett, 1973), but they
show a delay in exhibiting the e m o t i o n a l response (i.e., till eye o p e n i n g
and some m o t o r c o m p e t e n c e ) , because it makes little evolutionary sense
to exhibit such noisy behavior as DVs until one is sufficiently mature to
have some credible means to get out of harm's way. Thus, a l t h o u g h they
can obviously generate physical distress calls before their eyes open (for
example, when exposed to a cold e n v i r o n m e n t ) , true social separation
D V s - - n a m e l y those that occur even in a warm, soft, and n o n d a n g e r o u s
e n v i r o n m e n t - - d o not begin till a b o u t 3 weeks of life (Gurski, Davis, &
Scott, 1980). Once developed, these animals exhibit DVs well into puberty.
H u m a n babies tend to follow a similar p a t t e r n - - t h e e m o t i o n a l re-
sponse takes a while to mature, till a b o u t 8 months of age, w h e r e u p o n it
is evident for many years. Because h u m a n s are one of the most n e o t e n o u s
species on the face of the earth (i.e., we have a remarkably long child-
h o o d ) , we can also u n d e r s t a n d why strong feelings of loneliness can con-
tinue for a lifetime. On the o t h e r hand, rats, also born altricial like dogs
and h u m a n s , exhibit a b o u t an 8-day delay in the exhibition of true sepa-
ration calls, but then only emit t h e m for a short period of a week or two,
during which time they also d e m o n s t r a t e a brief period of true attach-
m e n t to their m o t h e r s and nest sites. These patterns p r e s u m a b l y reflect
the m a t u r a t i o n of certain brain systems, such as corticotropin-releasing
factor (CRF) systems, which are known to p r o m o t e this e m o t i o n a l re-
sponse (Panksepp, Normansell, H e r m a n , Bishop, & Crepeau, 1988).
However, for our purposes, the key question m i g h t be, what causes
this e m o t i o n a l response to decline in all species as a function of matura-
tion? We can be fairly certain that the most obvious explanation is not
applicable to the case: The DV circuitry itself does not degrade, because
one can electrically stimulate the diencephalic and mesencephalic trajec-
tories of the system to re-evoke infantile separation calls even when ma-
ture animals no longer a p p e a r to use this response system in their natural
behavioral repertoire ( H e r m a n & Panksepp, 1981). One obvious alterna-
8 Jaak Panksepp and Anesa Miller

tive possibility is sexual maturation, and the activation of the pituitary-


gonadal system. We have evaluated the role of this factor in guinea pigs
(Figure 1), and it does seem that testosterone secretion increases the
threshold of this system in males. The age-related decline in DVs was di-
minished by castration, and testosterone administration has also proven
quite effective in speeding the decline in birds (Panksepp, 1985b). Ovari-
ectomy and estrogen administration were not as effective. Thus, it seems
that the vigor of this emotional response is controlled to some extent by
male hormones and gonadal maturation, both of which presumably pro-
mote an asocial form of psychobehavioral independence. On the other
hand, females may remain more d e p e n d e n t on social contacts. If this is
so, it may explain why adult males tend to be more socially aloof than fe-
males, whereas females tend to have stronger social networks and appear
more socially interdependent than males. The paradox with this view is
that in humans the loss of a spouse has more devastating consequences for
a husband than a wife (see Melnechuk, 1988). Of course this may only be
a surface paradox, for the greater social networks of a woman may allow
her to ride through the grief of loss more effectively than males, whose
networks are commonly weaker and often emotionally more superficial.
However, we presently know little about the underlying physiological
mechanisms, although higher cognitive mechanisms clearly become in-
creasingly important in determining how adult humans respond to loss.
Contrary to earlier beliefs, cortical development is now known to
continue well into adulthood (Benes, 1994). The cortex can inhibit, con-
strain, and channel subcortical processes. Our assumption is that in the
mature organism the separation distress system still helps elaborate feel-
ings of loneliness, but that the output is channeled into instrumental be-
haviors that can help establish social contact. For instance, older organ-
isms, having had many prior experiences with separation, can cognitively
buffer the immediate absence of social companions with the confidence
that reunion will occur at some fairly predictable future time. As our
brains develop into maturity and beyond, cognitive abilities can come to
outweigh simple emotional ones. Conversely, changes in higher brain
functions in old age may again release subcortical functions, leading once
more to the prevalence of certain emotional e n e r g i e s ~ f e e l i n g s of frus-
tration, anger, and loss. Of course, such issues need to be experimentally
clarified.

B. P L A Y and D O M I N A N C E Systems
The development of PLAY also exhibits an inverted U-shaped func-
tion, whereby the intensity and frequency of rough-and-tumble activities
ESB-DVs from DORSOMEDIAL THALAMUS
70

60

50

40

30
Z
O
I'-- 20
,,r MALE-CONTROL
N
m
..J MALE-CASTRATED
"~
(J 10 ---0--" FEMALE-CONTROL "e
O --- O - - FEMALE-OVARIECTOMIZED
I I I
0
u') 7-10 11-14 15-18
I,M
tv
I-
u) ESB-Elicited DVs from PREOPTIC AREA
N 70
i1 ....................... O..................... O

O 60
>.
r
z
u.I 50
::)
O
I,M
Iz:
lie
40

30

20

10

7-10 11-14 15-18

AGE AT TESTING (Weeks)

Figure 1. Average brain stimulation elicited distress vocalizations (DVs) in guinea pigs as
a function of age and gonadal status from two separate sites within separation distress cir-
cuitry (i.e., dorsomedial thalamus and preoptic area). Male and female animals were surgi-
cally p r e p a r e d at least 1 week before testing, and current-intensity curves were run during
the three points in early d e v e l o p m e n t - - l a t e "childhood," ( 7 - 1 0 weeks), late juvenile period
( 1 1 - 1 4 weeks), and early adulthood ( 1 5 - 1 8 weeks of age). The data depicted represent re-
sults for the highest current level, constant at all ages. Clearly, electrical stimulation of the
brain (ESB)-elicited DVs declined as a function of age, and the decline was decreased by go-
nadectomy in both males and females. These data indicate that the maturation of gonadal
h o r m o n e systems promotes a decline in the responsivity of the separation distress system of
the brain (Sahley & Panksepp, 1983).
10 Jaak Panksepp and Anesa Miller

diminishes as animals enter late "childhood" and even more as they pro-
ceed through puberty (Panksepp, 1993; Panksepp, Siviy, & Normansell,
1984). We do not know what controls this decline, even though, again,
testosterone is a participant, because it can reduce juvenile playfulness
(Panksepp, 1989). Because we assume that the underlying play circuits
are a major source of the joy that organisms experience in social inter-
actions, we have had some interest in seeing whether we might be able to
resurrect play in its declining days using neurochemical manipulations.
For a synopsis of that work, see section V.
Although there is little empirical evidence on the functions of play,
it is likely that this activity exercises the brain systems that mediate
various social skillsmfor instance, how to win or lose gracefully and how
to handle oneself in competitive situations. Thus, rough-and-tumble play
seems to be a source process for social dominance and submission,
which are social issues that do not undergo significant decline as a func-
tion of age. Indeed, it is possible that among primates, as an individual
grows older, dominance emerges as much from playful, mutually positive
and beneficial i n t e r c h a n g e m f r o m the establishment of friendships and
c o a l i t i o n s ~ a s from brute force and intimidation. Indeed, analysis of
dominance in primate societies suggests that elevations of brain sero-
tonin can promote dominance (Raleigh, McGuire, Brammer, Pollack, &
Yuwiler, 1991) but not simply through an increase in aggression. Rather,
the establishment of confident and positive social relationships with
other members of the group allows the individuals with pharmacologi-
cally elevated serotonin activity to prevail. In rat societies, the animals
that have exhibited the highest levels of friendly juvenile play also tend
to be dominant. (Adams & Boice, 1989). It seems that juvenile playful-
ness paves the way to dominance.
In this context, it is also noteworthy that most h u m a n societies have
provided outlets for the vigorous expressions of playful dominance urges,
including medieval jousting and m o d e r n sports. The respect that these
forms of stylized play enjoy from powerful elderly humans (especially
males), including administrators of our universities, not to mention the
members of the business community who wrangle to purchase sport fran-
chises, testifies to the importance of play-dominance circuits in h u m a n
affairs. Even when one's own natural ability to express those urges has
markedly diminished, the symbolic value of supporting sport events at-
tests to the continuing powerful role of such motivations in h u m a n af-
fairs. We suspect the attraction of those activities t h r o u g h o u t the life
span, especially in aging males, reflects the fact that the PLAY systems of
the brain, which inspire young animals to frolic in youth, are the progen-
itors of systems and abilities that help mediate dominance in adult social
CHAPTER 1 Emotions and the Aging Brain 11

systems. Even when the urge to frolic has diminished, the symbolic power
and status urges have not.

C. LUST Systems of the Brain


Male and female brains are organized differently during the fetal pe-
riod to mediate gender characteristic sexual proclivities (Kinckl, 1990).
Robust sexual urges develop at puberty during the activational phase of
neurosexual development only if the p r o p e r patterns of h o r m o n e secre-
tion occur (Crews, 1987; LeVay, 1993). Such erotic urges reflect the mat-
uration of sexually dimorphic LUST systems, which remain partially dis-
tinct, and partially overlapping in males and females (Archer & Hansen,
1991). With aging, a hormonally related decline in sexual vigor occurs in
all species, but the rate of decline is related to each animal's sexual history
and also to the degree of encephalization of each species. For instance,
in sexually experienced male rats sexuality declines within several weeks
after castration, but in humans who have suffered the same fate, vitality
can continue for years (Archer & Hansen, 1991; Crews, 1987). Apparently,
thoughts can sustain sexuality when hormones have diminished, but it is
possible that these feats of h o r m o n e - i n d e p e n d e n t abilities are also due to
sustained neural changes of a noncognitive variety. The sustaining effect
of past experiences is most evident when hormonal decline is gradual, as
in the case of natural aging.
Although sexual habit structures can sustain sexuality in the absence
of the hormonal forces that initially drove these energies in earlier years,
they will not continue indefinitely in most species without those an-
cient physiological forces. Since the decline of sex hormones is generally
earlier and more precipitous in females than in males in most species,
sexual receptivity also declines earlier in females. However, this is not
obligatory in humans, where sexuality has been liberated to some extent
from immediate sex-hormonal influences by virtue of serving functions
other than mere reproduction, such as long-term social bonding, with
the resultant sharing of material resources and other defenses against
misfortune.
Moreover, in h u m a n females, persistent sexual desires are more
closely linked to the production of adrenal androgens than in other
species (Burger, Hailes, Nelson, & Menelaus, 1987; Morris, Udry, Khan-
Dawood, & Dawood, 1987). This suggests quite a different underlying or-
ganization for female eroticism in humans than the other mammalian
species, whose urges d e p e n d on the spontaneously cycling cascades of es-
trogen and progesterone. Because various n e u r o p e p t i d e circuits of the
brain are known to promote sexuality, including vasopressin, oxytocin,
12 Jaak Panksepp and Anesa Miller

and LH-RH (Pedersen, Caldwell, Jirikowski, & Insel, 1992), it will be of


great interest to determine how the responsivity of these systems declines
and the extent to which they remain resilient in old age.
In any event, the restoration and smooth functioning of the sexual
apparatus is greatly enhanced by appropriate h o r m o n e supplementation
in humans (Burger et al., 1987; Morris et al., 1987). It can also be restored
in animals by direct h o r m o n e administration into specific parts of the
brain: Injections of testosterone into the preoptic area restores male sex-
uality, and estrogen followed by progesterone into lower brain stem
structures restores female urges (Crews, 1987). Recent work has focused
on the development of pharmacological aids for restoring sexual ardor
in humans as it declines with age (Riley & Wilson, 1994). Animal data
suggest the potential utility of dopamine facilitators, for instance mono-
amine oxidase-B (MAO-B) inhibitors such as deprenyl as discussed in
section VI.D.

D. The A C C E I ~ A N C E System(s)
In addition to the brain systems discussed above, the emotion we
commonly call love is also closely related to the parental ACCEPTANCE sys-
tems. In all mammals, nurturance is mediated by distinct brain circuits
(Numan, 1988), but it is also remarkably susceptible to the influences
of various peripheral hormonal processes and learning (Krasnegor &
Bridges, 1990; Winberg & Kjellmer, 1994). How many distinct brain sys-
tems should actually be subsumed in this category remains in doubt, but
in lower animals the maternal components of nurturant behavior are be-
ing well delineated (Krasnegor & Bridges, 1990; Numan, 1988). In labo-
ratory rats nurturant tendency can be monitored simply via measures of
"sensitization" or "concaveation." These terms designate the induction of
maternal behaviors (nest building, pup retrieval, and hovering over the
pups) in virgin rats, both male and female, via prolonged exposure to rat
pups. Although males exhibit some nurturance (Brown, 1986), gener-
ally, mature females exhibit faster sensitization than males. Likewise,
during a brief period of life (perhaps corresponding to the most intense
"doll-play phase" of h u m a n children), juvenile rats exhibit a high level of
nurturance, with no major difference between males and females. How-
ever, with the onset of puberty and adulthood, sensitization proceeds
more slowly in males than females, although homosexual male rats re-
main as responsive as females (see Krasnegor & Bridges, 1990; Signoret,
Fabre-Nys, & Balthazart, 1994), suggesting that an adaptive value of this
phenotype may be to reduce reproduction and facilitate nurturance un-
der stressful circumstances.
CHAPTER 1 Emotions and the Aging Brain 13

Once sensitized, virgin animals exhibit very rapid onset o f n u r t u r a n c e


on subsequent occasions, indicating the potential power of learning fac-
tors. Thus, it is not surprising that females who have already had one lit-
ter are better mothers the second time around. Of course, we must be
cautious in concluding that this is a mere learning effect, for it remains
possible that the previous experiences have modified the arousability
of genetic mechanisms, such as the expression of oxytocin-based brain
chemistries within nurturant circuits of the brain, an effect that has
been observed in various rodent social models (Pedersen et al., 1992).
Also, it is known that a single birth can have long-term biochemical con-
sequences on the mothers' physiology, for instance, the levels of certain
h o r m o n e s such as prolactin and d i h y d r o e p i a n d r o s t e r o n e (Key, Pike,
Wang, & Moore, 1990).
In sum, the more experiences an individual has had with nurturance,
the more likely these mechanisms are to remain responsive in old age,
which probably helps make parents who have had many children excel-
lent grandparents. It will be most interesting to see how the underlying
neural systems, such as those that elaborate oxytocin, change as a func-
tion of development, and how these changes are modified by various so-
cial histories (Insel, 1992).

E. On the Nature of Social Bonding


The developmental nature of social b o n d i n g is probably directly re-
lated to the responsivity of ACCEPTANCE, LUST, PLAY, and PANIC sys-
tems, as discussed elsewhere (Panksepp, in press). W h e t h e r there is also
a separate social-bonding system i n d e p e n d e n t of the a f o r e m e n t i o n e d
neural substrates is not known. No d o u b t there are several distinct types
of social bonding; those that occur in infancy and c h i l d h o o d are neuro-
physiologically distinct from those that occur in puberty and early adult-
hood, whereas the friendships of old age can surely be based more on cog-
nitive factors than on elementary affective ones. However, without the
continued participation of the affective substrates, it is hard to imagine
that such relations could provide adequate satisfaction. Probably the
quality of bondings during the earlier phases of life helps determine the
responsivity of b o n d i n g systems in old age.
Probably the same chemistries that are i m p o r t a n t in decreasing
separation-distress responses and facilitating nurturant responses, namely
e n d o g e n o u s brain opioid, oxytocin, and prolactin systems, will be essen-
tial ingredients in the construction of social-bonds (Panksepp, 1991). It
should be informative to eventually determine, t h r o u g h the use of ani-
mal models, whether the underlying neural substrates of the earlier bond-
14 Jaak Panksepp and Anesa Miller

ing mechanism continue to control attachments in old age. Likewise,


some of these systems have been shown to be important in the construc-
tion of social memories (Winslow, Hastings, Carter, Harbaugh, & Insel,
1993), and it will be important to determine how such abilities change as
a function of age.

E The S E E K I N G ~ E X P E C T A N C Y or "I W A N T " System


This brain system, sometimes called an "appetitive motivational" or
"behavioral activation" system, mediates certain desires and interests that
are especially energized in youth, but the "energies" of which gradually
decline t h r o u g h old age. This system promotes active e n g a g e m e n t with
the w o r l d m e x p l o r a t i o n , investigation, and the anticipation of the re-
wards to be had in our environments (Panksepp, 1986, 1991). This sys-
tem is confluent with ascending brain d o p a m i n e systems, which course
from midbrain zones such as the ventral tegmental area to the basal gan-
glia and forebrain, in a broad trajectory from which the most vigorous
forms of self-stimulation and exploratory arousal are evoked with local-
ized electrical and chemical stimulation of the brain. The fact that this
system helps mediate that mysterious process that psychologists call posi-
tive reinforcement, in yet u n f a t h o m e d ways, adds further weight to the
thesis that the power of emotional systems in youth can p r o m o t e learn-
ing that lasts a lifetime.
By the mere application of electrical stimulation to this circuit or ad-
ministration of psychologically addictive drugs such as cocaine and the
amphetamines, one can permanently increase the sensitivity of this sys-
tem (Kalivas & Stewart, 1991). This also occurs in humans, not only be-
cause of psychostimulant abuse, but probably because of the incentive
sensitizing effects of life stressors and avaricious lifestyles (Robinson &
Berridge, 1993). When these systems become sensitized, organisms tend
to assume a more chronic craving mode, which makes them more sus-
ceptible to the various psychological addictions and materialistic desires
whose persistence and increasing prevalence creates m u c h havoc and
unhappiness in m o d e r n society. Massive overarousal of these systems,
in the presence of yet other neuropathologies, may contribute to those
strong paranoid tendencies that are diagnosed as adult-onset or func-
tional schizophrenias. Mild overarousal of these systems probably con-
tributes to various types of personality disorders.
Because d o p a m i n e is at the heart of this system, serving a c o m m a n d
influence, we have an excellent neurochemical marker for the decline of
the system with aging. Brain d o p a m i n e gradually diminishes in aging
rats, and similar patterns are evident in h u m a n s (Rogers & Bloom, 1985).
The decline in d o p a m i n e leads to the general decline in p s y c h o m o t o r
CHAPTER 1 Emotions and the Aging Brain 15

arousal as organisms age. The loss of vitality in brain d o p a m i n e systems is


also responsible for the onset of mild Parkinsonian symptoms in m a n y
older adults.
Because this system is vital for the motivational energy of many be-
havioral acts, it is especially i m p o r t a n t to find ways to counter its natural
decline. This has now b e e n achieved with the sustained administration of
deprenyl, and as discussed below, such treatment provides one way to
counteract the decline in mental energies as one ages. Because brain
d o p a m i n e circuits are readily sensitized by chronic exposure to psychos-
timulants and environmental stressors (Robinson & Berridge, 1993), it
will be i m p o r t a n t to evaluate how the vigor of sensitization changes as a
function of aging. W h e n we learn how to reverse such n e u r o e m o t i o n a l
habits of the animal brain, we will have some insight into controlling
afflictions that may accumulate with age in h u m a n s such as addictive per-
sonality and posttraumatic stress disorders (PTSD). On the other hand,
p e r h a p s sensitization decreases spontaneously with the aging process,
and thereby contributes to the "wisdom" of age. Indeed, we would not be
surprised if a decline in sensitization m i g h t be p r o m o t e d by positive so-
cial activities and chemistries such as discussed in the previous section,
but those possibilities r e m a i n to be empirically evaluated.

G. T h e F E A R System
All m a m m a l s have a f u n d a m e n t a l FEAR system in the brain, which
courses between amygdaloid, medial hypothalamic, and central gray
areas of the m i d b r a i n (Panksepp, 1991). Manifestations of this system
e m e r g e during early h u m a n d e v e l o p m e n t and have been reasonably well
characterized. H u m a n babies are afraid of falling before they are afraid
of darkness, and they fear darkness before they fear snakes and other
scary animals (Gray, 1987). The ability to cope with fears also probably be-
comes ever m o r e efficient as organisms grow older, thanks largely to the
d e v e l o p m e n t of cognitive strategies (i.e., the buffering effect of repre-
sentations of the past and future). It is possible that older animals' in-
creasing ability to remove themselves from harm's way simply allows for
lower activation of the FEAR system as organisms mature. This disuse ef-
fect could also be r e p r e s e n t e d in the brain as a gradual weakening of the
synaptic connectivities and chemistries of the FEAR system, but that is
not an established fact.
Although we know almost n o t h i n g a b o u t changes in the FEAR system
as a function of aging, one i m p o r t a n t issue to be considered is the ability
of this system to also b e c o m e sensitized as a function of experience. T h e r e
is suggestive evidence that this occurs, as appears to take place in PTSD.
Fear sensitization can be evoked simply by electrically stimulating the
16 Jaak Panksepp and Anesa Miller

headwaters of the FEAR system in the amygdala, which leads to increased


permeability of neural pathways to medial hypothalamic components of
the FEAR system (Adamec, 1990).
A chronic increase in fearfulness can also be induced by various anx-
iogenic drugs, especially those "inverse agonists" that promote anxiety by
interacting with the benzodiazepine receptor system. These manipula-
tions generate a personality change in experimental animals, whereby
formerly friendly animals become chronically hyperdefensive (Adamec,
1990). No one has yet determined whether this increase in "limbic per-
meability" changes with age, or whether it can be more effectively allevi-
ated at certain phases of development than others. It will be important to
address these neuropsychiatric issues in future research because they
may have implications for treating anxiety disorders in the elderly.

H. The RAGE System


It is difficult to analyze the status of this basic neural system with-
out direct brain manipulations (Bandler, 1988; Siegel & Pott, 1988).
H u m a n s are usually trained to inhibit their anger in public, and there
are no good scales to measure the ongoing influence of this system in
the daily affairs of humans or animals. However, it is a commonplace
observation that humans generally tend to become less volatile as they
age, and there are animal data to suggest that high circulating levels of
gonadal steroids and hypothalamic releasing factors generally tend to
reduce the thresholds of aggression systems (Bermond, Mos, Meelis,
van der Poel, & Kruk, 1982; Inselman-Temkin & Flynn, 1973). Thus, in a
m a n n e r similar to declining h o r m o n e - d e p e n d e n t sexual urges, it seems
likely that there are age-related declines in the arousability of the RAGE
system.
As with the FEAR system, one can sensitize the RAGE system (Ada-
mec, 1990), but the underlying neural mechanisms remain to be clari-
fied. It is possible that despite the decline in the system as one ages, older
organisms have more habitual "trigger spots" in such circuits, and if so, it
will be especially important to determine how they might be muted with
cognitive, affective, pharmacological, and other somatic interventions.

IV. B R A I N C H A N G E S IN O L D AGE

A. Neuroanatomical Issues
The various forms of neural deterioration that characterize aging are
an object of active study. The neuropathologies underlying the most se-
CHAPTER 1 Emotions and the Aging Brain 17

vere age-related mental disordersmAlzheimer's, Parkinson's, and Hun-


tington's disease--have now been well characterized, and there is increas-
ing medical hope for some of them (Parks, Zec, & Wilson, 1993). Each of
these disorders entails emotional changes: Alzheimer's is associated with
confusional states that can lead to frustration and anger; Parkinson's,
with the inability to become actively engaged with world affairs; and
Huntington's, with a gradual dissolution of behavioral coherence, so that
various emotions can more readily rise to the surface, even t h o u g h ma-
ture people would normally tend to keep their stronger feelings in the
background.
There is hope that some of the neural deficits of these disorders,
along with the consequence of various forms of cerebral ischemia, can
be r e d u c e d and prevented with new medicines, although most work
along those lines remains in the experimental stages (Ginsberg, 1995).
There are strategies for administering n e u r o n a l growth factors to delay
cell death, and dietary maneuvers that can reduce the influence of free-
radical damage to n e u r o n a l systems (Mendell, 1995; Russell, 1995). Even
surgical procedures, such as fetal tissue grafts and nerve growth factor
infusions into the brain have been attempted (Olson et al., 1992). Most
importantly though, as described in the next section, there are some
neurochemical manipulations that can help preserve the fading vitality
of the aging brain.

B. Neurochemical and Neurophysiological Issues


There is a b u n d a n t evidence that various neurochemical systems de-
cline as a function of age. Probably the best characterized are those re-
lated to the diseases m e n t i o n e d in the previous section: there is loss of
p r o m i n e n t basal forebrain cholinergic and cortical somatostatin in Alz-
heimer's that may be due to specific genetic infirmities (Strittmatter &
Roses, 1995); there is basal ganglia d o p a m i n e loss in Parkinson's (Wich-
mann, Vitek, & DeLong, 1995), and loss of all of the i n t e r n e u r o n chem-
istries of the basal ganglia in Huntington's (Young, 1995). The various
changes associated with these afflictions are well detailed in many sources.
A characterization of the decline in specific n e u r o p e p t i d e chemistries
that mediate specific emotional and motivational tendencies (Panksepp,
1993) remains to be conducted, but it seems likely that most systems lose
vitality with age. In general, the aging brain tends to exhibit more slow-
wave activity during waking, which reflects a less arousable brain. Simi-
larly, PET scans for glucose metabolism are able to predict the onset of
Alzheimer's symptoms by m o n i t o r i n g the early decline of metabolic ac-
tivity (Kennedy et al., 1995). One of the major lines of future research
will be to determine how specific systems can be restored so as to increase
18 Jaak Panksepp and Anesa Miller

the quality of life for aging individuals. As we will see in the next section,
important progress is being made.

V. THE N E U R O C H E M I C A L F O U N T A I N S OF YOUTH:
SLOWING THE CHANGES OF OLD AGE

The resilience and activity of most neurochemistries decline as a func-


tion of age (Rogers & Bloom, 1985). No physician can prescribe the road
to a vital and happy old age, but without sufficient joy, energy, health,
and sustained good nights' sleep, happiness is difficult to achieve. Qual-
ity of life can be enhanced by meaningful activities, close friends and few
enemies, but in addition to these self-evident factors, the incommensu-
rate biological declines in different bodily systems can be coaxed in posi-
tive directions through the wonders of modern chemistry.
There are now several simple beneficial neurochemical approaches
to some of the mood and motivational problems that characterize aging.
In addition to generally beneficial metabolic/nutritional manipulations,
several neuroendocrine systems can be safely treated to yield general
health benefits: brain dopamine (Knoll, 1992), pineal melatonin (Miles,
Philbrick, & Thompson, 1989), adrenal dehydoepiandrosterone (Regel-
son, Loria, & Kalimi, 1988), and other h o r m o n e supplements. All three
of the above decline gradually during the process of aging. Facilitation of
each of these systems can prolong the life span in animals, and there is
no evidence that any supplement is harmful if used properly as prophy-
lactic agents.

A. Melatonin and Sleep


Some of the sleep difficulties that accompany aging may result from
the decline of melatonin. Recently, this pineal h o r m o n e has emerged as
a powerful sleep-promoting molecule that can be orally taken, and con-
tinues to have reliable effects for extended periods with no significant
side effects. Indeed, this molecule offers a great number of positive effects
that can promote general health, such as synchronizing bodily rhythms,
increasing immune competence, reducing tumor growth, and alleviating
psychiatric ailments such as depression, anxiety, and perhaps even some
psychotic symptoms (Miles et al., 1989). For those who might not be able
to get to sleep because of loneliness, it is worth noting that the molecule
is quite effective in reducing separation distress (Nelson, Panksepp &
Ikemoto, 1994), and one of the most exciting effects is its ability to in-
CHAPTER 1 Emotions and the Aging Brain 19

crease the life span, which has now been observed u n d e r various condi-
tions (Regelson et al., 1988).

B. The Dehydroepinadrosterone Story


D e h y d r o e p i n a d r o s t e r o n e (DHEA) manufactured in the body from
cholesterol, is the most a b u n d a n t adrenal h o r m o n e in the body that de-
clines dramatically as a function of aging, but its normal physiological
function remains uncertain. Some have characterized DHEA as a "buffer
h o r m o n e " that seems to broadly facilitate the smooth functioning of many
bodily systems (Regelson et al., 1988). In the brain, which has an endoge-
nous DHEA system, it promotes m e m o r y processes, apparently by a re-
duction of GABA activity (Flood, Morley, & Roberts, 1992). Oral supple-
mentation with the h o r m o n e in aging individuals can have various
beneficial effects on the body, ranging from a reduction in cholesterol to
a diminished incidence of heart attacks. In the present context, it is note-
worthy that a m o n t h of oral supplementation markedly increased the
overall sense of well-being of middle-aged adults (Morales, Nolan, Nel-
son, & Yen, 1994). In addition to general health effects, this may partially
reflect the ability of this agent to exert a mild antianxiety effect, which
has been d o c u m e n t e d in animal models (Melchior & Ritzmann, 1994).

C. Deprenyl and Sexual and Cognitive Vitality


As mentioned, brain d o p a m i n e systems gradually die off as individu-
als age. The decrease in d o p a m i n e is one of the major reasons that active
engagement with the world diminishes in old age, ranging from decreased
sexual desire to the loss of other lifelong interests. Indeed, animal re-
search shows that one of the predictors of death in male animals is their
loss of sexual vigor (Knoll, 1988).
It is known from in vivo neurochemical studies that brain d o p a m i n e
is plentifully released in animals when they are sexually aroused (Pfaus &
Phillips, 1991). Thus, it was natural for investigators to ask whether
sexual behavior could be restored by restoring brain d o p a m i n e activity.
Since d o p a m i n e is normally destroyed in n e u r o n s by the B-variant of the
enzyme MAO, an investigator in H u n g a r y decided to determine if inhi-
bition of the enzyme with a drug called deprenyl would restore sexuality
in aging male rats (Knoll, 1988). Indeed, long-term administration of
low-levels of the drug proved quite effective in maintaining the sexual in-
terests and abilities of older rats. Instead of declining sexual activity at
their normal old age, the deprenyl-treated animals continued to copulate
for several additional months (the equivalent of several years in h u m a n
20 Jaak Panksepp and Anesa Miller

terms). Indeed, deprenyl-treated animals lived longer than expected, and


this was not simply due to the fact that they were having m o r e sex.
Apparently deprenyl can protect the metabolic decay of d o p a m i n e
systems in the brain. Although we do not know for certain, the restored
neuropsychic vitality may well be the critical ingredient in sustaining life.
Moreover, it should be emphasized that this effect reflected a true in-
crease in the n o r m a l life span of the animals. It was not due to m o r e ani-
mals simply reaching the maximal extent of their life expectancy: Most
individuals were living longer than what would normally be expected. Of
course, we do not yet know w h e t h e r this effect will be evident in h u m a n s
(there has not yet been time to complete such an e x p e r i m e n t ) , but be-
cause the drug is available for other disorders, some are optimistically
c o n s u m i n g deprenyl with the assumption that the rats' good fortunes
will transfer to the h u m a n condition. We do know that deprenyl can pre-
vent the decline of d o p a m i n e n e u r o n a l death in h u m a n s as it does in an-
imals, and hence it is presently used medically to forestall severe Parkin-
sonian symptoms during the early phases of the disease (Parkinson Study
Group, 1989). It also appears to be beneficial in reducing cognitive
deficits in Alzheimer-type individuals (Agnoli, Fabbrini, Fioravanti, &
Martucci, 1992). T h e r e are b o u n d to be many other such prophylactic
treatments as the chemical dynamics of the m a m m a l i a n brain are m o r e
fully revealed. However, rather than trying to summarize the details of
the many other e m e r g i n g systems in the limited space available here, let
me summarize one general strategy by which our lab has sought to un-
d e r s t a n d m s o far without m u c h s u c c e s s m h o w m i g h t one sustain emo-
tional vitality as a function of aging? We have sought n e u r o c h e m i c a l fac-
tors to sustain playfulness.

D. In Search of the Ludic Cocktail~Joy Extension


In our estimation, no other e m o t i o n a l system in the brain can pro-
duce as m u c h pure joy as that which elaborates rough-and-tumble play
(Panksepp et al., 1984; Panksepp, 1993). This brain system is m o d u l a t e d
by opioids, a m o n g the most pleasurable molecules in the brain (Panksepp
et al., 1985), and by a host of other chemistries, only some of which have
been identified (Panksepp, Normansell, Cox, Crepeau, & Sacks, 1987).
As discussed above, ludic urges decline as a function of aging, but a sub-
stantial degree of playfulness remains in h u m a n s and some o t h e r neote-
nous species t h r o u g h o u t their lives. Presumably, young children have
special brain chemistries that sustain open, childlike attitudes toward ex-
istence, but we do not know what they are.
CHAPTER 1 Emotions and the Aging Brain 21

Although our search for that fountain of youth has m e t with only
m o d e s t success, let us briefly summarize what we have done. A m o n g the
first p h a r m a c o l o g i c a l manipulations that we evaluated on play were drugs
that affect the major biogenic-amine s y s t e m s m n a m e l y those of serotonin,
n o r e p i n e p h r i n e , and d o p a m i n e - - a s well as those that affect brain opi-
oids. We f o u n d that we could marginally increase play with (a) low doses
of broadly acting serotonin-receptor antagonists such as methysergide,
(b) low doses of a p o m o r p h i n e that reduce brain d o p a m i n e activity, and
(c) low doses of opiate-receptor agonists such as m o r p h i n e (Panksepp
et al., 1984, 1987). Accordingly, we p r o c e e d e d to evaluate each of these,
as well as all combinations of these agents, to see if we could reinvigorate
playfulness when it was declining during late puberty. Unfortunately,
none of these agents alone nor in any combination restored playfulness
in young adults.
We have not given up the quest. One possibility we are presently eval-
uating is the recently identified e n d o g e n o u s c a n n a b a n o i d system of the
brain (Childers, Sexton, & Roy, 1993), and we have had some success in
restoring playfulness as rats age (Pruitt & Panksepp, 1995). Of course, it
remains possible that no n e u r o p h a r m a c o l o g i c a l agent shall ever restore
full juvenile playfulness. The decline in play may reflect a deterioration
of circuits that c a n n o t be resurrected no matter what we do, or it may
reflect the decline in the genetic expression of certain play chemistries
that c a n n o t be rejuvenated without great advances in our ability to ma-
nipulate genetic expression. Of course, we will continue the quest, for it
is a worthy journey.

VI. C L O S I N G R E M A R K S

M o d e r n neuroscience is b o u n d to provide aids that can make the


natural j o u r n e y of aging a m o r e positive experience than it has been in
the past. The above examples are only the tip of an iceberg of useful
knowledge that is being revealed by m o d e r n neuroscience. The moral
and ethical choices this kind of knowledge will confront us with are
many. What should be our choices when we know how to m a n i p u l a t e in-
dividual emotions? Will it be a reasonable choice to give people medi-
cines that can turn off discrete types of fear, anger, and loneliness, and
those that turn on playfulness, nurturance, and a sense of u n i o n with oth-
ers? What will be our choices when we are eventually able to provoke
feelings of love and sorrow i n d e p e n d e n t l y of the many life events that
normally access these natural systems of the brain?
22 Jaak Panksepp and Anesa Miller

T h e s e will be difficult decisions for society to h a n d l e . S o m e will


surely say that we s h o u l d leave the e m o t i o n a l mysteries alone. T h e y are
too p o w e r f u l to t a m p e r with. We s h o u l d live o u t o u r lives in the old ways,
in the midst of the joys a n d frustrations of o u r families as well as in the
midst o f the pain a n d sorrow that old age has always b r o u g h t . O t h e r s will
be m o r e enthusiastic for the useful alternatives that science will provide.
H o p e f u l l y m o d e r n cultural a n d societal t h o u g h t will c o n t i n u e to m a t u r e
so as to assure e a c h the r i g h t to c o m p l e t e t h e i r life j o u r n e y as p e a c e f u l l y
or vibrantly as they wish.

ACKNOWLEDGMENTS

This work was supported in part National Institutes of Health (NIH) grant
R15 HD30387, and The Memorial Foundation for Lost Children, Bowling Green,
OH 43402.

REFERENCES

Adams, N., & Boice, R. (1989). Development of dominance in domestic rats in


laboratory and seminatural environments. Behavioural Processes, 19, 127-142.
Adamec, R. E. (1990). Kindling, anxiety and limbic epilepsy: Human and ani-
mal perspectives. In J. A. Wada (Ed), Kindling 4. Advances in behavioral biology
(pp. 329-341). New York: Plenum Press.
Agnoli, A., Fabbrini, G., Fioravanti, M., & Martucci, N. (1992). CBF and cognitive
evaluation of Alzheimer type patients before and after MAO-B treatment:
A pilot study. European Neuropsychopharmacology, 2, 31 - 35.
Almli, C.R., & Golden, G. T. (1974) Infant rats: Effects of lateral hypothalamic
destruction. Physiology & Behavior, 13, 81-90.
Archer, T., & Hansen, S. (Eds.) (1991). Behavioral biology: Neuroendocrine axis.
Hillsdale, NJ: Lawrence Erlbaum Associates.
Bandler, R. (1988). Brain mechanisms of aggression as revealed by electrical and
chemical stimulation: Suggestion of a central role for the midbrain peri-
aqueductal grey region. In A. N. Epstein & A. R. Morrison (Eds.), Progress
in psychobiology and physiological psychology (Vol. 13, pp. 67-154). New York:
Academic Press.
Barkow, J. H., Cosmides, L., & Tooby, J. (Eds.) (1995). The adapted mind: Evolution-
ary psychology and the generation of culture. New York: Oxford University Press.
Benes, F. M. (1994). Development of the corticolimbic system. In G. Dawson &
K. W. Fisher (Eds.), Human behavior and the developing brain (pp. 176-206).
New York: The Guilford Press.
Bermond, B., Mos, J., Meelis, W., van der Poel, A. M. & Kruk, M. R. (1982). Ag-
CHAPTER 1 Emotions and the Aging Brain 23

gression induced by stimulation of the hypothalamus: Effects of androgens.


Pharmacology Biochemistry & Behavior, 16, 41-45.
Brown, R. E. (1986). Paternal behavior in the male Long-Evans rats (Rattus
norvegicus). Journal of Comparative Psychology, 43, 36-42.
Burger, H., Hailes, J., Nelson, J., & Menelaus, M. (1987). Effect of combined im-
plants of estradiol and testosterone on libido in postmenopausal women.
British Medical Journal, 294, 936-939.
Childers, S. R., Sexton, T., & Roy, M. B. (1993). Effects o f a n a n d a m i d e on cannabi-
noid receptors in rat brain membranes. Biochemical Pharmacology, 47, 711-
715.
Crews, D. (Ed.). (1987). Psychobiology of reproductive behavior. An evolutionary per-
spective. Englewood Cliffs, NJ: Prentice-Hall, Inc.
Flood,J. F., Morley, J. E., & Roberts, E. (1992). Memory-enhancing effects in male
mice of pregnenolone and steroids metabolically derived from it. Proceeding
of the National Academy of Sciences, 89, 1567-1572.
Ginsberg, M. D. (1995). Neuroprotection in brain ischemia: An update (Part II).
The Neuroscientist, 1, 164-175.
Gray, J. A. (1987). The psychobiology of fear and stress (2nd. ed). Cambridge, UK:
Cambridge University Press.
Gurski, J. C., Davis, K., & Scott, J. P. (1980). Interaction of separation discomfort
with contact comfort and discomfort in the dog. Developmental Psychobiology,
13, 463-467.
Herman, B. H., & Panksepp, J. (1981). Ascending endorphinergic inhibition of
distress vocalization. Science, 211, 1060-1062.
Insel, T. R. (1992). Oxytocin: A neuropeptide for affiliation-evidence from be-
havioral, autoradiographic and comparative studies. Psychoneuroendocrinol-
0gy, 17, 3-35.
Inselman-Temkin, B., & Flynn, J. P. (1973). Sex-dependent effects of gonadal and
gonadotropic hormones on centrally-elicited attack in cats. Brain Research, 60,
393-410.
Kalivas, P., & Stewart, J. (1991). Dopamine transmission in the initiation and ex-
pression of drug- and stress-induced sensitization of motor activity. Brain Re-
search Reviews, 16, 223-244.
Kennedy, A. M., Frackowiak, R. S.J., Newman, S. K., Bloomfield, B. M., Seaward,
J., Roques, P., Lewington, G., Cunningham, V. J. & Rossor, M. N. (1995).
Deficits in cerebral glucose metabolism demonstrated by positron emission
tomography in individuals at risk of familial Alzheimer's disease. Neuroscience
Letters, 186, 17- 20.
Key, T. J. A., Pike, M. C., Wang, D. Y. & Moore, J. W. (1990). Long term effects of
a first preganancy on serum concentrations of dehydroepindrosterone sul-
fate and dehydroepindrosterone. Journal of Clinical Endocrinology and Metabo-
lism, 70, 1651-1653.
Kinckl, F. A. (1990). Hormone toxicity in the newborn. Berlin: Springer-Verlag.
Knoll, J., (1988). Extension of lifespan of rats by long-term ( - ) d e p r e n y l treat-
ment. Mount Sinai Journal of Medicine, 55, 67-74.
24 Jaak Panksepp and Anesa Miller

Knoll, J., (1992). (-)Deprenyl-medication: A strategy to modulate the age-re-


lated decline of the striatal dopaminergic system. Journal of the American Geri-
atric Society, 40, 839-847.
Kolb, B., & Whishaw, I. Q. (1990). Fundamental ofhuman neuropsychology (3rd ed).
New York: W. H. Freeman & Co.
Krasnegor, N. A., & Bridges, R. S. (Eds.). (1990). Mammalian parenting: Biochemi-
cal, neurobiological and behavioral determinants. New York: Oxford University
Press.
LeVay, S. (1993). The sexual brain. Cambridge, MA: MIT Press.
MacLean, P. D. (1990). The triune brain in evolution. New York: Plenum Press.
Melchior, C. L., & Ritzmann, R. F. (1994). Dehydroepindrosterone is an anxiolytic
in mide on the plus maze. Pharmacology Biochemistry & Behavior, 47, 437-441.
Melnechuk, T. (1988). Emotions, brain, immunity, and health: A review. In
M. Clynes &J. Panksepp (Eds.),Emotions and psychopathology (pp. 181-247).
New York: Plenum Press.
Mendell, L. M. (1995). Neurotrophic factors and the specification of neural func-
tion. The Neuroscientist, 1, 26-34.
Miles, A., Philbrick, D. R. S., & Thompson, C. (Eds.). (1989). Melatonin: Clinical
perspectives. Oxford: Oxford University Press.
Morales, A., Nolan,J.J., Nelson,J. C., & Yen, S. S. C. (1994). Effects of replacement
dose of dehydroepindrosterone in men and women of advancing age. Jour-
nal of Clinical Endocrinology and Metabolism, 78, 1360-1367.
Morris, N., Udry, J., Khan-Dawood, F., & Dawood, M. (1987). Marital sex frequency
and midcycle female testoterone. Archives of Sexual Behavior, 16, 27-37.
Nelson, E., Panksepp, J., & Ikemoto, S. (1994). The effects of melatonin on isola-
tion distress in chickens. Pharmacology, Biochemistry, & Behavior, 49, 327-333.
Numan, M. (1988). Maternal behavior. In E. Knobil &J. D. Neill (Eds.), Thephys-
iology of reproduction (pp. 1569-1645). New York: Raven Press.
Olson, L., Nordberg, A., von Holst, H., Backman, L., Ebendal, T., Alafuzoff, I., Am-
beria, K., Hartvig, P., Herlitz, A., Lilja, A., Lundqvist, H., Langstrom, B., Mey-
erson, B., Persson, A., Viitanen, M., Winblad, B., & Seiger, A. (1992). Nerve
growth factors affects 11C-nicotine binding, blood flow, EEG, and verbal
episodic memory in an Alzheimer patient (Case Report). Journal of Neural
Transmission, 4, 79-95.
Panksepp, J. (1982). Toward a general psychobiological theory of emotions. The
Behavioral and Brain Sciences, 5, 407-467.
Panksepp, J. (1985a). Mood changes. In P. J. Vionken, G. W. Bruyn, & H. L.
Klawans (Eds.), Handbook of clinical neurology Vol. 1. (45). Clinical Neuropsy-
chology (pp. 271-285). Amsterdam: Elsevier Science Publishers.
Panksepp, J. (1985b). Testosterone promotes the decline of separation-induced distress
vocalizations in young domestic chicks. Unpublished data.
Panksepp, J. (1986). The anatomy of emotions. In R. Plutchik & H. Kellerman
(Eds.), Emotion: Theory, research and experience: Vol. 3, Biological foundations of
emotions (pp. 91-124). San Diego, CA: Academic Press.
Panksepp, J. (1989). Testosterone promotes the decline in playfulness in juvenile rats.
Unpublished data.
CHAPTER 1 Emotions and the Aging Brain 25

Panksepp, J. (1991). Affective neuroscience: A conceptual framework of the neu-


robiological study of emotions. In K. T. Strongman (Ed.), International Re-
view of Studies on Emotion (Vol. 1, pp. 59-99). Chichester, UK: John Wiley.
Panksepp, J. (1993). Rough and tumble play: A fundamental brain process. In
K. MacDonald (Ed), Parent-child play: Descriptions and implications (pp. 147-
184). New York: SUNY Press.
Panksepp, J. (in press) Affective neuroscience: The foundations of human and animal
emotions. New York: Oxford Univ. Press.
Panksepp, J., Jalowiec, J., DeEskinazi, F. G., & Bishop, P. (1985). Opiates and play
dominance in juvenile rats. Behavioral Neuroscience, 99, 441-453.
Panksepp, J., Knutson, B., & Pruitt, D. L. (in press). Toward a neuroscience of
emotion: The epigenetic foundations of emotional development. In M. F.
Mascolo & S. Griffin (Eds.), What develops in emotional development? New York:
Plenum Press.
Panksepp, J., Normansell, L., Cox, J. F., Crepeau, L.J., & Sacks, D. S. (1987). Psy-
chopharmacology of social play. In B. Olivier, J. Mos, & P. F. Brain (Eds.),
Ethopharmacology of agonistic behaviour in animals and humans (pp. 132-144).
Dordrecht, Holland: Martinus Nijhoff Pubs.
Panksepp, J., Normansell, L., Herman, B., Bishop, P., & Crepeau, L. (1988).
Neural and neurochemical control of the separation distress call. InJ. D. New-
man (Ed.), The physiological control of mammalian vocalization (pp. 263-299).
New York: Plenum Press.
Panksepp, J., Siviy, S., & Normansell, L. (1984). The psychobiology of play: Theo-
retical and methodological perspectives. Neuroscience and Biobehavioral Re-
views, 8, 465-492.
Parkinson Study Group. (1989). Effect of deprenyl on the progression of disabil-
ity in early Parkinson's disease. The New England Journal of Medicine, 321,
1364-1371.
Parks, R. W., Zec, R. F., & Wilson, R. S. (Eds.). (1993). Neuropsychology of Alz-
heimer's disease and other dementias. New York: Oxford University Press.
Pedersen, C. A., Caldwell,J. D.,Jirikowski, G., & Insel, T. R. (Eds.). (1992). Annals
of the New York Academy of Sciences. Vol. 652. Oxytocin in maternal, sexual and so-
cial behaviors. New York: New York Academy of Sciences.
Pettijohn, T. F. (1979). Attachment and separation distress in the infant guinea
pig. Developmental Psychobiology, 12, 73-81.
Pfaus, J., & Phillips, A. (1991). Role of dopamine anticipatory and consummatory
aspects of sexual behavior in the male rat. Behavioral Neuroscience, 105,
727-943.
Pruitt, D., & Panksepp, J. (1995). Anandamine and synthetic cannabanoids can in-
crease play in young adult rats. Unpublished data.
Raleigh, M.J., McGuire, M. T., Brammer, G. L., Pollack, D. B., & Yuwiler, A. T.
(1991). Serotonergic mechanisms promote dominance acquisition in adult
male vervet monkeys. Brain Research, 559, 181-190.
Regelson, W., Loria, R., & Kalimi, M. (1988). Hormonal intervention: "Buffer
hormone" or "state dependency." Annals of New York Academy of Sciences, 521,
260-273.
26 Jaak Panksepp and Anesa Miller

Riley, A. J., & Wilson, C. (Eds.). (1994). Sexual pharmacology. New York: Oxford
Univ. Press.
Robinson, T., & Berridge, K. (1993). The neural basis of drug craving: An
incentive-sensitization theory of addiction. Brain Research Review, 18,
247-291.
Rogers, J., & Bloom, F. E. (1985). Neurotransmitter metabolism and function in
the aging central nervous system. In C. E. Finch & E. L. Schneider (Eds.),
Handbook of the biology of aging (pp. 645-691). New York: Van Nostrand Rein-
hold Co.
Russell, D. S. (1995). Neurotrophins: New players, clinical uses? The Neuroscien-
tist, 1, 119-122.
Sahley, T. L., & Panksepp, J. (1983). Effects of castration of prepubertal guinea pigs on
brain stimulation induced distress vocalizations. Unpublished data.
Scott, J. P., Stewart, J. M., & DeGhett, V.J. (1973). Separation in infant dogs. In
J. P. Scott & E. C. Senay (Eds.), Separation and depression: Clinical and research
aspects (Publ. 194). Washington, DC: American Association for the Advance-
ment of Science.
Siegel, A., & Pott, C. B. (1988). Neural substrates of aggression and flight in the
cat. Progress in Neurobiology, 32, 261 - 283.
Signoret, J. P., Fabre-Nys, C., & Balthazart, J. (Eds.). (1994). Hormone, brain and
behaviour. [Special Issue ] Psychoneuroendocrinology, 19, 403- 720.
Strittmatter, W. J., & Roses, A. D. (1995). Apolipoprotein E: Emerging story in
the pathogenesis of alzheimer's diseases. The Neuroscientist, 1, 298-306.
Wichmann, T., Vitek, J. L., & DeLong, M. R. (1995). Parkinson's disease and the
basal ganglia: Lessons from the laboratory and from neurosurgery. The
Neuroscientist, 1, 236- 244.
Wilhelmsson, M., & Larsson, K. (1973). The development of sexual behavior in
anosmic male rats reared under various social conditions. Physiology & Be-
havior, 11, 227-232.
Winberg, J., & Kjellmer, I. (Eds.). (1994). The neurobiology of infant-parent inter-
action in the newborn period. ACTA Paediatrica, 83, [suppl. 397].
Winslow, J. T., Hastings, N., Carter, C. S., Harbaugh, C. R., & Insel, T. R. (1993).
A role for central vasopressin in pair bonding in monogamous prairie voles.
Nature, 365, 544-548.
Young, A. B. (1995). Huntington's disease: Lessons from and for molecular biol-
ogy. The Neuroscientist, 1, 51-58.