Psychopharmacologia (Berl.
) 43, 233-237 (1975) - 9 by Springer-Verlag 1975
Influence of A9-Tetrahydrocannabinol
on Partial Reinforcement Effects
ADAM DREWNOWSKI* and JEFFREY A. GRAY
Department of Experimental Psychology, Oxford University, England
Received January 31, 1975; Final Version May 5, 1975
Abstract. Two experiments were performed with rats trained
with either continuous reinforcement (food) or random 50 ~
partial reinforcement for running in a straight alley. Half the
rats were trained with daily injections of 0.5 mg/kg ~19-tetra-
hydrocannabinol (THC) and half with vehicle injections,
all animals being extinguished with vehicle injections in
Key words: Ag-Tetrahydrocannabinol -- Partial Reinforcement Acquisition Effect - Partial Reinforcement Extinction Effect.
The effects of A 9-tetrahydrocannabinol (THC) have
Often been compared with those of barbiturates and
alcohol. A g-THC can have sedative and depressant
(Brown, 1972) as well as analgesic (Bicher and
Mechoulam, 1968) effects; it prolongs barbiturate
sleeping time in rats (Kubena and Barry, 1970) and
mice (Gill et al., 1970); it impairs motor and mental
performance in man in a manner similar to that of
alcohol (Hollister and Gillespie, 1970; Manno et at.,
1971); and cross tolerance between Ag-THC and
alcohol has been reported in the rat (Newman et al.,
1972). Anecdotal reports suggest, in addition, that
social marihuana use relieves frustration and a n x i e t y -
effects similar to those produced by mild alcohol
intoxication.
Earlier experiments with alcohol and sodium
amylobarbitone by N. E. Miller and co-workers estab-
lished that both these substances com~teract the
effects of punishment and improve performance which
has been inhibited by fear (Barry and Miller, 1962).
Both drugs also weaken the behavioural effects
of frustrative nonreward (Barry et al., 1962; Miller,
1964). Among these effects are the partial reinforce-
ment acquisition effect (PRAE), i.e. the higher asymp-
totic running speed reached in a straight alley by a
group of animals trained on partial reinforcement
(PRF) compared to a group trained on continuous
reinforcement (CRF), and the partial reinforcement
extinction effect (PREE), i.e. the greater resistance to
extinction displayed by P R F animals relative to C R F
* Present address: The Rockefeller University, New York,
N.Y. 10021, U.S.A.
Expt. 1 and with THC injections in Expt. 2. The partial
reinforcement acquisition effect was abolished by THC during
training; the partial reinforcement extinction effect was
abolished by THC either during training or during extinction.
In these respects THC resembles amylobarbitone and alcohol.
animals. The PRAE has been reported to be blocked
by both amylobarbitone (Wagner, 1963; Gray, 1969)
and alcohol (Nelson and Wollen, 1965), and the
PREE to be reduced (Ison and Pennes, 1969; Gray
and Dudderidge, 1971) or completely abolished (Gray,
1969, 1972) by amylobarbitone. In view of the simi-
larities between A 9-THC, alcohol and amylobarbitone
noted earlier, and the reported anti-frustrational
properties of marihuana, it might be expected that
A g-THC would also reduce the behavioural effects
of frustrative nonreward. We have tested this pos-
sibility by investigating the effects of A 9-THC on the
PRAE and PREE.
Experiment 1
The experimental design was essentially the same as
that used by Gray (1969, Experiment 1) in a study of
amylobarbitone, except that extinction was conducted
only with placebo injections.
Method. The subjects (Ss) were 32 male Wistar rats purchased
from Oxfordshire Laboratory Animal Colony. They were
gradually introduced to a 22-hrs food-deprivation schedule
during their first week in the laboratory, and were maintained
on this schedule throughout the experiments, being fed
approximately 1 hr after the last squad of the day was run.
Water was available ad lib. at all times in the home cage.
A fi'esh solution of A9-THC in Tween/saline was prepared
each day. Samples of stock solution of A9-THC in benzene
(1 ml/mg) were evaporated in a rotary evaporator at reduced
pressure and at a temperature of about 30~C. A double volume
of I mg/ml Tween 80 in acetone was then added and the
solution evaporated again, at which time the oily residue was
dissolved in physiological saline to make up the concentra-
tion of 0.5 mg/ml.
234 Psychopharmacologia (Bed.), Vol. 43, Fasc. 3 (1975)

The apparatus consisted ofa 1.2-m long straight aluminium o--o Placebo CRF
runway, 16 cm wide with walls 32 cm high. Two identical o---o Placebo PRF
0.5mg/kg Z~9-THCCRF
compartments 20 cm square with walls the same height as
e---o 05mg/kg A9-THC PRF
the runway, served as startbox and goalbox at either end.
The startbox allowed access to the runway via a door of clear 1.4 /%
plastic which the animal could nose downwards when the 1.2 GOAL / ~ c~
experimenter released a solenoid-operated catch, at the same ,0
time starting the first of three electronic timers used to measure 0.8 / ',
successively start, run and goal times to the nearest 0.01 sec. co
The first timer was stopped and the second started when the
animal crossed a photobeam located 15 cm from the startbox 0.Z:
~O--O, "O" ,O
door. The second timer was in turn stopped and the third one 1.2" RUN ,or 'b ,o--o
started when the animal crossed a second photobeam located -~ 1.0 '/
15 cm before the hand-operated guillotinetype goalbox door, 08 /
also made of clear plastic. This door was gently lowered ~ o.6 ~"
by the experimenter when the animal broke a third photobeam 0.4
(thus stopping the final timer) located 10 cm into the goalbox.
A small plastic food-cup (3.5 cm square and 1 cm high) was -~1.8" START ,P-'~176 N
secured to the floor in front of the rear goalbox wall. During 16 ,o' ',
~.~, ?",o-~ b--o,,,
the inter-trial intervals, each animal was kept in a small
individual waiting box. 1.2 ,iyr~;'~",,',~
On the first day of pretraining (10 days after arrival in the
0.8
laboratory) all animals were given a single i.p. injection of
0.6
saline and allowed 10 rain in the alleyway, in pairs, with food
ad lib. in the goal box. On the second day of pretraining, the
0.2
animals were individually introduced to the alleyway and
allowed a 5-rain session, again food ad lib. in the goal-box. 0" i ~ 5 i g g ~J/i ~ 5 i
On the third day, the animals were allowed to negotiate the Acquisition Extinction
DAYS
alley with doors being operated by the experimenter, and were
Fig. I. Progress of acquisition and extinction as a function of
allowed 1 min in the goal-box with ad lib. food. On the fourth
reinforcement schedule and acquisition drug treatment in
day of pretraining Ss were placed in the individual waiting
Expt. 1. All groups received placebo during extinction
boxes, and each was given two rewarded runs in the alleyway;
15 sec were allowed in the goal-box.
During acquisition proper, 8 trials a day were run for
8 days. The four experimental conditions during acquisition
(8 Ss each) were: CRF A9-THC; PRF A9-THC; CRF Results. Fig. 1 presents the course o f b o t h a c q u i s i t i o n
placebo; and PRF placebo. The PRF animals were rewarded a n d e x t i n c t i o n for the f o u r e x p e r i m e n t a l groups.
on the following schedule over two consecutive days ( + means D u r i n g a c q u i s i t i o n the p l a c e b o g r o u p s d i s p l a y e d
rewarded trial, - means non-rewarded trial): + - + - - a classic P R A E o f the k i n d d e s c r i b e d initially b y
+ + - ; - - + + + - - + . CRF animals were rewarded on
every trial. The reward consisted of four 54-mg food pellets. G o o d r i c h (1959) a n d H a g g a r d (1959): T h e P R F
Intertrial intervals were approximately 2 min, and Ss were run a n i m a l s r e t u r n e d faster speeds in the start a n d run,
in squads of 4, one from each experimental condition. Each b u t n o t the g o a l section, a n d this a d v a n t a g e b e c a m e
squad was run at approximately the same time each day. g r e a t e r as t r a i n i n g p r o c e e d e d a n d was g r e a t e r in the
Test sessions lasted about 30 min; 30 min before each one
s t a r t t h a n in the r u n section. In the d r u g g e d g r o u p s ,
began, Ss were given an i.p. injection of either 0.5 mg/kg
A9-THC in 0.5 mg/ml Tween 80/saline solution or an equiv- in c o n t r a s t , this P R A E does n o t a p p e a r . I n the start
alent volume of vehicle alone. The subject was removed from a n d r u n sections, b o t h d r u g g e d g r o u p s were a b o u t
the goal box as soon as he consumed the reward. On non- as fast as the p l a c e b o C R F g r o u p . In the g o a l section,
rewarded trials, the empty food cup was present in the box, the 2 d r u g g e d g r o u p s were b o t h slower t h a n the
and the animal was left in the goalbox for 15 sec.
2 p l a c e b o groups. Statistical analysis c o n f i r m e d this
In extinction (which began the day after acquisition was
complete) each group was injected with the vehicle only. picture.
Extinction lasted 4 days, using the same procedure as before In the start scores, the D r u g x R e i n f o r c e m e n t
but with the goal-box food-cup always empty for all groups. i n t e r a c t i o n was significant at the 0.05 level ( F = 4.1,
If a subject failed to enter the goal-box in 120 sec, he was d f = 1/28). F u r t h e r analysis b y t-test b a s e d on the
removed from the alleyway and this time was recorded. When a p p r o p r i a t e e r r o r t e r m f r o m the analysis o f v a r i a n c e
2 consecutive times of 120 sec were recorded, S was dropped
from the experiment, and this time was entered for all sub- s h o w e d the m e a n difference b e t w e e n the p l a c e b o C R F
sequent trials for the purpose of statistical analysis. The a n d P R F g r o u p s to be significant ( P < 0.05), while
results were submitted to analyses of variance (the variables t h a t b e t w e e n the d r u g C R F a n d P R F g r o u p s fell well
being Drug, Reinforcement and Days) separately for start, s h o r t o f significance. Similarly, there was a significant
run and goal sections of the alley and separately for acquisition
difference ( P < 0.01) b e t w e e n the P R F d r u g a n d
and extinction. F o r the extinction analyses, the last day of
acquisition was included as an estimate of acquisition asymp- p l a c e b o g r o u p s , b u t no reliable difference b e t w e e n
tote. All scores were converted to speeds (1/sec) before analysis. the C R F d r u g a n d p l a c e b o groups. T h u s the effect
A. Drewnowski and J. A. Gray: THC and Partial Reinforcement Effects
of A 9-THC in the start section is to prevent the in-
creased speed produced by partial reinforcement.
Similar conclusions apply to the run section, but
less firmly. The Drug x Reinforcement interaction felt
just short of the 5 }o level of significance (F = 3.7,
df = 1/28; P = 0.05 at F = 4.2). The appropriate
t-tests again showed that this reflected a significantly
greater running speed in the placebo PRF condition
relative to the placebo CRF (P < 0.02) and also
relative to the drug PRF condition (P < 0.001), the
other two relevant comparisons falling well short of
significance. In addition, there were significant inter-
actions between Drug and Days (F = 3.1, df = 6/168,
P < 0.01) and between Reinforcement and Days
(F = 2.2, df = 6/!68 , P < 0.05): As can be seen from
Fig. 1, these interactions reflect the fact that the
differences due both to the drug and to reinforcement
condition became larger as acquisition progressed.
In the goal section, Reinforcement had no signifi-
cant effects on speed, either alone or in interaction
with other variables. There was, however, a significant
Drug effect (F = 19.5, df = 1/28, P < 0.001) and a
significant interaction between Drug and Days (F = 3.0,
df= 6/168, P < 0.01). It is clear from Fig. 1 that
these significant effects arise because the A9-THC -
treated rats entered the goal more slowly than the
controls and this tendency became greater as training
proceeded.
Turning to the results in extinction, it is clear
from Fig. 1 that there was a PREE in the control
groups, but none in the animals which had been
drugged during training (though no longer during
extinction itself). These conclusions were supported
by the statistical analyses.
In the start section, there was a significant inter-
action between Drug and Reinforcement (F = 12.6,
df= 1/28, P < 0.01). Further analysis by t-test
showed that the control PRF group was significantly
faster than the control CRF group and also faster
than the drug P R F group (P < 0.001 in both cases).
The difference between the PRF and CRF groups
within the drug condition fell well short of significance,
as did the difference between the drug and placebo
groups within the CRF condition.
A highly similar interaction between Drug and
Reinforcement appeared in the run speeds (F = 8.9,
df = 1/28, P < 0.01), and the t:tests again showed
that this reflected the significant differences between
the placebo P R F group and both the placebo CRF
group and the drug P R F group (P < 0.001 in both
cases), the other two relevant comparisons being
nonsignificant. In the run section there was also a
significant interaction between Drug, Reforcement
and Days (F = 3.3, df = 4/112, P < 0.05). It is clear
fiom Fig. 1 that this triple interaction arises because
235
the placebo PRF group gets progressively more
different from the other three groups as extinction
continues.
In the goal sectio~n, there was once again a signif-
icant interaction between Drug and Reinforcement
(F = 5.5, elf= 1/28, P < 0.05), The t-tests again
showed this interaction to reflect the greater speed
of the PRF group relative both to the CRF placebo
group (P < 0.01) and to the PRF drug group
(P < 0.001), the other two relevant comparisons
being nonsignificant. It should be noted that the
significant difference during extinction between the
PRF and CRF groups within the placebo condition
in the goal section cannot merely reflect the continua-
tion of differences already present at the end of acquisi-
tion (as might be the case in the start and run section),
for the acquisition asymptotic speeds did not differ as a
function of reinforcement in the goal section (see
above). The analysis of the extinction goal speeds
also revealed significant interactions between Drug
and Days (F = 3.7, df= 4/112, P < 0.01) and be-
tween Reinforcement and Days (F = 4.9, df = 4/112,
P < 0.01). As can be seen in Fig. 1, the former of
these interactions reflects the fact that the difference
between the drug and placebo conditions present at
the end of acquisition grew smaller as extinction
continued. The Reinforcement x Days interaction
arises because, averaged across the two drug condition,
the advantage in speed of the PRF animals gets
greater as extinction proceeds (Fig. 1). It is somewhat
surprising that the triple interaction between Drug,
Reinforcement and Days is not significant (F = 1.5,
df= 4/112); but it is nonetheless clear from Fig. 1
that, in spite of the significant Reinforcement x Days
interaction, there is no PREE within the drug condi-
tion.
Discussion. The results of this experiment show that
A 9-THC, injected during acquisition but not extinc-
tion, completely blocks the appearance both of the
PRAE and of the PREE, resembling in these respects
both amylobarbitone sodium (Wagner, 1963; Gray,
1969, 1972) and ethanol (Nelson and Wollen, 1965).
Furthermore, as is the case with the latter two drugs,
this blockage is entirely due to a change in the animals
exposed to partial reinforcement, there being no
difference due to the drug within the CRF condition
(except in the goal section during acquisition and
during the first day of extinction when the A 9-THC
animals were slower than the placebo controls). It
is unlikely that the effects of A 9-THC observed in
this experiment are due to any motor incapacity.
During acquisition, both the CRF and the PRF groups
in the drug condition gained speed in the start and run
sections at the same rate as the CRF placebo animals;
while, during extinction, it would have been sufficient
236
for the PRF animals which had previously received
A 9-THC to continue performing as well as they had
performed at the end of acquisition for a PREE to
have occurred. The slower goal speeds returned by
the drugged animals irrespective of reinforcement
condition might reflect a motor impairment, but other
explanations are equally likely (e.g., a reduction in the
incentive effects of proximity to the goal).
One possible explanation of the abolition of the
PREE by A 9-THC during acquisition is that it is an
example of state-dependent learning (Overton, 1966);
though if so, it would be a peculiar example in that
the state-dependency would affect learning about
nonreward without affecting learning about reward.
However, this possibility can easily be tested by
conducting extinction under continued drug
administration. Expt. 2, therefore, was addressed to
this problem.
Experiment 2
Method. The experimental design repeated that of Expt. 1,
except that the 4 groups (CRF A9-THC, PRF A9-THC, CRF
placebo and PRF placebo) were all extinguished with in-
jections of A9-THC. The method was otherwise identical
to that used in Expt. 1. A new batch of experimentallynaive
rats served as Ss. Extinction lasted only 3 days (instead of 4),
since it progressed more rapidly in this experiment.
Results. Fig. 2 displays the course of acquisition and
extinction for the 4 groups.
The effects of partial reinforcement on acquisition
performance were much less evident in the placebo
groups of this experiment than in Expt. 1. The general
pattern was the same but did not achieve statistical
significance. Only in the run section was there a signif-
icant interaction between Drug and Reinforcement
(F = 4.7, df = 1/28, P < 0.05). This interaction re-
flected the fact that A 9-THC significantly reduced
running speed only in PRF animals (P < 0.05),
CRF animals running nonsignificantly faster in the
drug than in the placebo condition.
Turning to extinction, the striking feature of the
results is the total absence of a PREE in either the
drug or the placebo condition on any of the measures,
start, run or goal. The results displayed in Fig. 2 show
this clearly for the groups trained and extinguished
on A 9-THC. For the groups trained on placebo and
extinguished on A9-THC the graphic presentation
of the results makes it appear that a residual enhanced
resistance to extinction was present in the PRF group.
However, the statistical analyses failed to confirm
this. On neither the start nor the run measure was
Reinforcement significant, either as a main effect or
in interaction with Drug or Days. On the goal measure,
there was a significant Reinforcement x Days inter-
action (F = 4.6, df = 3/84, P < 0.01). However,
Psychopharmacologia (Berl.), Vol. 43, Fasc. 3 (1975)
inspection of the relevant means indicated that this
was largely due to the faster goal speeds of the CRF
groups on the final day of acquisition (which was
included in the extinction analyses). This superiority
had disappeared by the first day of extinction. Al-
though the PRF animals were marginally faster on
the second day of extinction (P = 0.05 by t-test),
by the final day of extinction the two reinforcement
conditions were indistinguishable from each other.
At best, therefore, a very small PREE remained.
The only other significant results of interest in the
analysis of the extinction results were two interactions
between Drug and Days in the run and goal sections
(F = 3.5 and 3.8, respectively, d f - - 3/84, P < 0.05).
On both measures the groups switched from placebo
to drug were returning faster speeds on the final day
of acquisition and then extinguished more rapidly
than the groups which were on drug during both
acquisition and extinction.
Discussion. While the PRAE took the same general
form in Expt. 2 as in Expt. 1, it was not significant.
This is not very surprising as the PRAE is known to
be a much less robust phenomenon than the PREE.
The only significant effect of A 9-THC during acquisi-
t i o n - a reduction in run speed confined to PRF ani-
m a l s - replicates the same finding in Expt. 1. However,
the absence of a PRAE in the placebo groups renders
this finding more ambiguous than the corresponding
one in Expt. 1.
The most striking feature of the results of Expt. 2
was the minimal effect which partial reinforcement
had on resistance to extinction even in the groups
trained on placebo. Given the general robustness of
the PREE and the fact that a large PREE was obtained
in the placebo groups trained under identical condi-
tions in Expt. 1, this result is almost certainly due
to the one important difference in the design of the
two experiments: namely, that in Expt. 1 extinction
was conducted with placebo injections, while in Expt. 2
it was conducted under the drug. Thus it appears that
A 9-THC injected during extinction reduces the PREE
almost to vanishing point. A similar, but less complete,
reduction in the PREE is produced by amylobarbitone
injections during extinction (Gray, 1969).
Expt. 2 also discounts the possibility that the results
of Expt. 1 represent a form of state-dependent learning
(Overton, 1966). Animals both trained and extin-
guished under A 9-THC showed as complete an absence
of the PREE in this experiment as did animals trained
on drug but extinguished on placebo in Expt. 1.
Owing to the fact the animals trained on placebo and
extinguished on drug also failed to show a signif-
icant PREE (as discussed above), it is not possible
to state definitely that A9-THC given in training
A. Drewnowski and J. A. Gray: THC and :Partial Reinforcement Effects 237

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and drug actiorb H. Steinberg, ed., pp. 1-18. London:
grateful to N. McNaughton for help with the statistical
Churchill (Ciba Foundation, Symposium)
analyses and to Dr. E. W. Gill for supplying the drugs used.
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Adam Drewnowski, Department of Experimental Psychology, Oxford University, South Parks Road, Oxford 0X1 3PS, England