Accepted Manuscript

Hormones and the Coolidge effect

Elisa Ventura-Aquino, Alonso Fernández-Guasti, Raúl G. Paredes

PII: S0303-7207(17)30493-8
DOI: 10.1016/j.mce.2017.09.010
Reference: MCE 10070

To appear in: Molecular and Cellular Endocrinology

Received Date: 18 April 2017

Revised Date: 8 September 2017
Accepted Date: 9 September 2017

Please cite this article as: Ventura-Aquino, E., Fernández-Guasti, A., Paredes, Raú.G., Hormones and
the Coolidge effect, Molecular and Cellular Endocrinology (2017), doi: 10.1016/j.mce.2017.09.010.

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 ACCEPTED MANUSCRIPT
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Hormones and the Coolidge effect

Elisa Ventura-Aquino1,2, Alonso Fernández-Guasti2 and Raúl G. Paredes1

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Instituto de Neurobiología, Universidad Nacional Autónoma de México; Querétaro,

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México
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Departamento de Farmacobiología, CINVESTAV-Sede Sur; México

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Corresponding author:
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Elisa Ventura-Aquino,
Instituto de Neurobiología
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Universidad Nacional Autónoma de México

Juriquilla, Querétaro. México
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Tel (52) 4422381060

e-mail: eliventura@outlook.com
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Abstract

The Coolidge effect is the renewal of sexual behavior after the presentation of a novel

sexual partner and possibly occurs as the result of habituation and dishabituation processes.

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This re-motivation to copulate is well studied in males and is commonly related to sexual

satiety, which involves several neurobiological changes in steroid receptors and their

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mRNA expression in the CNS. On the other hand, there are few reports studying sexual

novelty in females and have been limited to behavioral aspects. Here we report that the

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levels of rat proceptive behavior, a sign of sexual motivation, declines after 4 h of

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continuous mating, particularly in females that were unable to regulate the time of mating.
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Such reduction was not accompanied by changes in lordosis, suggesting that they were not

due to the vanishing of the endocrine optimal milieu necessary for the expression of both
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components of sexual behavior in the female rat. These and previous data support important

differences between sexual behavior in both sexes that would result in natural divergences
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in the Coolidge effect expression. We here also review some reports in humans showing
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peculiarities between the pattern of habituation and dishabituation in women and men. This

is a growing research field that needs emphasis in female´s subjects.

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Key words: The Coolidge effect, female sexual behavior, male sexual behavior, sexual
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novelty.
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Introduction

Sexual behavior is a feasible way to study the mechanisms through which hormones

and neurotransmitters converge in neural systems. Due to its evolutionary importance for

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survival, sexual behavior is highly-conserved in mammals (Paredes, 2014). For this reason,

there are similarities between the neurobiology of sexual behavior among species. One

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consistent phenomenon, related to sexual behavior, is the resumption of mating induced by

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a novel sexual partner (Bermant et al., 1968; Dewsbury, 1981; Lucio et al., 2014).

Although largely reported in males (Wilson et al., 1963; Bermant et al., 1968; Brown,

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1974; Rodriguez-Manzo, 1999; Lucio et al., 2014; Lucio et al., 2017), the study of the
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Coolidge effect in females is a relatively new area and a growing field of research (Lisk &

Baron, 1982; Ventura-Aquino et al., 2016).

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The term Coolidge effect was coined by a research group, led by the behavioral
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endocrinologist Frank A. Beach, derived from an anecdotal event, which veracity has not

been confirmed (Wilson et al., 1963; Ågmo, 2007). The 30th president of the United States,
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Mr. Calvin Coolidge and his wife made a separate tour during a visit to a large farm. When
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Mrs. Coolidge was in the chicken’s area, she noted that a rooster mated repeatedly; she

asked the guide “how many times the rooster mated in a day?”, and the guide answered
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“dozens of times”. Mrs. Coolidge asked the guide to notice that to Mr. President. When Mr.
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Coolidge arrived to the henhouse, the guide did. The president remained silent, thought for

a moment and asked if the rooster mated with the same hen every time, the guide replied

negatively. Mr. President requested the guide “tell that to Mrs. Coolidge” (Ågmo, 2007).

Although extensive studies have evaluated the Coolidge effect in males (Dewsbury,

1981; Lucio et al., 2014), the concept has been only recently extended to females and
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therefore, it is necessary a wider definition that involves both sexes. Thus, the Coolidge

effect could be defined as the renewal of motivational and appetitive components of sexual

behavior due to sexual novelty, after mating repeatedly with a single partner. In the

following sections, we will describe various aspects of the Coolidge effect in both sexes in

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experimental animals and an approximation in humans.

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For the present review we conducted on line searching on scientific indexed

journals data bases such as Scopus, PubMed and Science, filling in the search field:

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“Coolidge effect”, “sexual habituation”, “sexual satiety” and “males” or “females” and

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their combination. We restricted the search to scientific areas but we considered results
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with no limitation of dating or document type. However, using this initial searching filter

some results did not fit with our criteria, in these cases, we considered articles related with
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sexual behavior focused on mammals.

The Coolidge effect in non-human males

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The Coolidge effect has been extensively studied in males of many species (Tlachi-

López et al., 2012; Lucio et al., 2014), including primates (Michael & Zumpe, 1978) and
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almost always related to sexual satiation, defined as the sexual inhibition induced by

repeated copulation (Phillips-Farfán & Fernández-Guasti, 2009). A male rat may copulate
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repeatedly with a single female until becoming sexually exhausted. This satiation involves
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three stages: development, complete inhibition of mating and recovery, which seem to be

underlied by endocrine, neurobiological and behavioral mechanisms. Figure 1 depicts the

temporal course of sexual satiety and the timing when the Coolidge effect occurs in the

male rat. Most studies (Rodríguez-Manzo & Fernández-Guasti, 1995; Phillips-Farfán et al.,

2007; Phillips-Farfán & Fernández-Guasti, 2009; Rodríguez-Manzo et al., 2011) have used
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a paradigm that involves continuous mating with a single female for 4h, during which the

male copulates for around 150 min and stays sexually inactive (without an additional

ejaculation) for 90 min. This inactive period is the criterion to establish sexual satiety. If

during it or immediately after, an unknown sexually receptive female is presented, the male

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resumes mating and that is known as the Coolidge effect. The large majority of studies

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(Rodríguez-Manzo & Fernández-Guasti, 1994; 1995; Fernández-Guasti & Rodríguez-

Manzo, 2003) have done pharmacological manipulations 24-48 hours later, when the

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inhibition of sexual behavior is considered maximal because the presence of an unknown

female fails to elicit sexual behavior. That is, the Coolidge effect can be induced only

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immediately after the male has reached sexual satiety, but not 24 or 48 h later. Three days
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later, the males begin to recover (Romano-Torres et al., 2007; Rodríguez-Manzo et al.,

2011). The restoration of full sexual activity performance depends on the sexual satiety
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paradigm (Larsson, 1956) and is achieved around fifteen days after the male reached sexual
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exhaustion (Beach & Jordan, 1956). The sexual inhibition that characterizes satiety is
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related to neurobiological changes that are widely described elsewhere (Fernández-Guasti

& Rodríguez-Manzo, 2003; Phillips-Farfán & Fernández-Guasti, 2009). To mention some

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data, males rats that ejaculate twice, four times or until achieving sexual exhaustion, present

a similar increase of c-Fos-immunoreactivity (IR) positive cells in the bed nucleus of the
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stria terminals (BNST), the medial amygdala (Me AMG), the medial preoptic area
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(MPOA), and the nucleus accumbens (NA) (Phillips-Farfán & Fernández-Guasti, 2007).

Although these reports are made in male rats, there is a similar pattern of c-Fos-IR

expression after sexual activity in other species such as the Syrian hamster (Parfitt &

Newman, 1998). However, there are some brain areas where c-Fos is differentially

expressed in sexually satiated males, independently of the number of ejaculations before

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sexual satiation, such as the piriform cortex, the anterodorsal and the posteroventral Me

AMG; and the lateral septum, denoting their possible participation in the establishment of

sexual satiety (Phillips-Farfán & Fernández-Guasti, 2007). The augment of c-Fos-IR

expression indicates an immediate neuronal activation of these brain areas, that seems

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independent of the amount of sexual activity required to reach the inhibitory stage (Phillips-

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Farfán & Fernández-Guasti, 2007).

It is possible that the initial neuronal activation triggers other changes during

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continuous mating until achieving sexual satiation. For example, in the MPOA, a relevant

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region that regulates male sexual behavior (Paredes & Agmo, 1992; Paredes, 2003), 24 h
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after a single ejaculation, there is a reduction in androgen receptor (AR) and its mRNA,

with no changes in the estrogen receptor subtype α (ER-α), nor its mRNA (Phillips-Farfán
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et al., 2007; Fernández-Guasti et al., 2010). Whereas successive ejaculations -until sexual

satiation- reduced even more the values of AR and its mRNA, accompanied by an increase
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in the ER-α and its mRNA in the MPOA (Fernández-Guasti et al., 2003; Phillips-Farfán &
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Fernández-Guasti, 2007; Fernández-Guasti et al., 2010). Protein and genetic expression

modifications should not be generalized between brain areas, for instance, in the
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ventromedial hypothalamic nucleus (VMN), where a single ejaculation failed to modify AR

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or ER-α expression, sexual satiety reduced AR with no changes in ER- α (Phillips-Farfán et

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al., 2007; Fernández-Guasti et al., 2010). It is worth mentioning that these adaptations in

rats and other species are unrelated to variations in serum gonadal hormones (Phillips-

Farfán & Fernández-Guasti, 2009; Fernández-Guasti et al., 2010; He et al., 2013) .

There is also a bulk of studies analyzing the inhibition of mating during sexual

satiety by employing pharmacological manipulations that reverse or retard such inhibition.

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For example, the systemic administration, 24 h after sexual satiation, of drugs that affect

various neurotransmitter systems, such as naloxone, apomorphine, yohimbine, 8-hydroxy-

2-(di-n-propylamino) tetralin (8-OH-DPAT) or anabolic androgens, affect sexual satiation

(Rodríguez-Manzo & Fernández-Guasti, 1994; Mas et al., 1995; Rodríguez-Manzo &

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Fernández-Guasti, 1995; Romano-Torres et al., 2007). However, as aforementioned if

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sexually exhausted males, are exposed to an unknown female 24 h after sexual satiety, they

do not renew mating, suggesting that the neurotransmitters involve in the reversal of sexual

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satiety by pharmacological treatments are different from those underlying the Coolidge

effect. In this regard, Dennis Fiorino and colleagues (2007) evaluated dopamine (DA)

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levels in the NA by in vivo microdialysis during mating until satiation and during the
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Coolidge effect in male rats (Fiorino et al., 1997). Dopamine is relevant because it

participates in the motivational components of behaviors that the animal predicts as

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rewarding, such as mating (Berridge & Robinson, 1998). They found an initial increase in
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DA levels in the NA during mating with a female that returned to basal levels when the
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male attained sexual exhaustion. Whereas DA remained low if the initial female was

relocated in the mating arena, when the male was exposed to an unknown female, DA
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levels in the NA peaked again (Fiorino et al., 1997). These results indicated that DA is

important for the sexual motivation renewal that characterizes the Coolidge effect.
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Following that idea, Rojas-Hernández and colleagues evaluated the effect of systemic
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administration of bromocriptine, a D-2 receptors agonist, on sexual behavior in male rats

immediately after sexual satiation, an important methodological difference with the

aforementioned reports (Rojas-Hernández & Juárez, 2015). They found that bromocriptine

restarted sexual behavior with the same female, mimicking the Coolidge effect. In addition,

there are reports in various species such as rams, rats and human males showing facilitatory
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effects of bromocriptine on sexual behavior (Ambrosi et al., 1977; Doherty et al., 1981).

Bromocriptine, in addition to its dopaminergic effects, decreases prolactin secretion, a

hormone that inhibits sexual behavior (Doherty et al., 1981; Drago, 1984; El-Beheiry et al.,

1988; Krüger et al., 2002). Dopamine would regulate that the incentive value for a novel

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sexual partner increases after habituation, as Fiorino and colleagues described (Fiorino et

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al., 1997).

For the establishment of the Coolidge effect, it is to be expected the participation of

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other mediators that regulate individual recognition, mainly for species which chemosignals

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and olfactory cues are important for social recognition such as rodents. In this regard, we
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found that sexually satiated males and controls had similar c-Fos density in the piriform

cortex, suggesting that it may participate in the olfactory recognition of the female partner
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during the initial mating bouts and/or the Coolidge effect (Phillips-Farfán & Fernández-

Guasti, 2009). In addition, Aras Pertrullis (2003) reported that male hamsters with
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ibiotenic lesions in the perirhinal-entorhinal cortex, fail to discriminate between novel and
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familiar sexual partners (Petrulis & Eichenbaum, 2003). The importance of chemosignals

on the discrimination is important also for other species, i.e., in burying beetles, the male
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impregnates pheromones to females during mating that serve to recognize novel sexual
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females and therefore the Coolidge effect expression in this species (Steiger et al., 2008).
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Finally, it is worth mentioning that along decades it was thought that genetic diversity of

the offspring was the main biological consequence of the Coolidge effect (Jennions &

Petrie, 2000). This concept, however, has been modified by recent studies showing that its

putative biological aim is related with male reproductive competition (Tlachi-López et al.,

2012; Lucio et al., 2014; Lucio et al., 2017).

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The Coolidge effect in non-human females

Contrary to the extensive research on males, there are few reports of sexual satiety

and the effect of a novel sexual partner in females, although it is well recognized that males

influence females’ neuroendocrine and reproductive functions in diverse species (Bruce,

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1960; Colmenares & Gomendio, 1988). It would not be surprising that some of these

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effects involve changes on sexual motivation and therefore, is plausible the expression of

the Coolidge effect in females. Notwithstanding, it has to be recall that there are obvious

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discrepancies between the sexual behavior features in both sexes that may result in a

different expression of the Coolidge effect. For example, the female sexual behavior in

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rodents depends on ovarian hormones during the proestrous phase of the estrus cycle; or by
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exogenous hormonal replacement in ovariectomized females (Blaustein & Erskine, 2002;

Blaustein, 2009). Additionally, rat feminine sexual behavior presents two main
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components, receptivity and proceptivity. Receptivity is a dorsiflexion reflex, mainly

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estrogen-dependent (Blaustein, 2009), that exposes the vaginal entrance and facilitates the
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penis intromission. Proceptivity, encompass a series of species-specific behaviors displayed

by sexually receptive females that indicate the readiness to mate. Proceptive behaviors are
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facilitated by progesterone (Fernández-Guasti et al., 1991). In female rats, there are two

main proceptive behaviors, ear wiggling and hop-darting (Erskine, 1989). Although still
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controversial, some authors consider proceptive behaviors to reflect sexual motivation

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(Erskine, 1989; Rössler et al., 2006; Graham & Pfaus, 2013; Ventura-Aquino & Fernández-

Guasti, 2013a). As aforementioned, there is growing interest in studying this field including

the evaluation of both components of the female sexual response during sexual novelty

(Ågmo, 1999; Ågmo et al., 2004; Ventura-Aquino & Fernández-Guasti, 2013b).

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Robert Lisk and Gregory Baron (1982) reported for the first time the presence of the

Coolidge effect in females (Lisk & Baron, 1982). They measured the lordosis duration in

hamsters in proestrus during a mating test with a male. Once females achieved the sexual

satiety criterion (15 minutes with no lordosis and aggressive behaviors towards the male),

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the male was replaced by another one. Females resumed lordosis until once more they

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achieved the sexual satiety criterion. They continued replacing up to four males. Females

displayed lordosis to every male, although with a shorter duration than that shown to the

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precedent. Authors concluded that the lordosis resumption with unknown males was a

manifestation of the Coolidge effect in females. Afterwards, Gillian Lester and Boris

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Gorzalka (1988) employed a similar paradigm but instead of using a new male every time,
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they presented, at the third replacement, an unknown male, or that with which the female

had previously copulated. Females only resumed lordosis with the unknown male (Lester &
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Gorzalka, 1988).
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Additionally, there are some reports evidencing the Coolidge effect in female rats in
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two mating conditions, paced and non-paced mating (Ågmo, 2007; Ventura-Aquino &

Fernández-Guasti, 2013b; Ventura-Aquino et al., 2016). In the paced mating (PM)

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condition, the female is able to regulate the time of sexual interactions. This is achieved by
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employing a mating cage divided in two compartments by a mesh with a little hole through
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which only the female can freely pass due to its smaller size than that of the male. Whereas

in non-paced mating (NPM), there is no division and therefore the female cannot avoid

sexual approaches from the male (Paredes & Vazquez, 1999).

In a PM paradigm, females copulated with a single male until achieving the sexual

exhaustion criterion that consisted of 20 minutes during which the female did not cross to
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the male’s compartment, it took about three to five ejaculations (Ågmo, 2007). After that

period, the male was replaced for an unknown one, or removed for a moment and relocated

in the mating arena. Remarkably, females displayed more proceptive behaviors and entered

faster when the unknown male was placed, than when the first male was reintroduced

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(Ågmo, 2007). Our research group evaluated proceptive and receptive behaviors, in females

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in proestrus, elicited during 90 minutes of continuous mating with a male. This period was

selected in order to avoid the male’s sexual satiety that would affect the female’s behavior.

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After this interval, the initial male was replaced with a second unknown male, and that

couple was allowed to mate for a second interval of 90 minutes (Ventura-Aquino &

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Fernández-Guasti, 2013b). We found that proceptive behaviors declined along the first 90
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min of mating with the initial male in both copulating conditions -PM and NPM-, but only

females that regulated mating showed an upturn in hop-darting when a second unknown
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male was presented, whereas lordosis behavior was unaffected. Using this paradigm,
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proceptive behaviors eventually declined after 180 minutes of mating (90 min with each
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male). Under these testing conditions, we assumed that the upturn in proceptivity -produced

by the unknown male- could have prevented the complete extinction of these behaviors. For
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this reason, we evaluated the frequency of proceptive behaviors, also in female rats in

proestrus, during 4 hours of continuous mating with a single male in both copulating
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conditions: PM and NPM. We hypothesized that proceptivity would extinguish as a

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possible indicator of female sexual satiety. As shown in figure 2, females presented a

notable decrease in proceptive behaviors along 4 hours of continuous mating, particularly

under the NPM condition. In PM, however, the levels of proceptivity remained stable until

the last series. Lordosis was maintained at maximum levels without time modifications in

PM and NPM (both conditions with a median of 100 along the whole test). These high and
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continuous levels of lordosis exclude the possibility that the decrease in proceptivity was

due to the vanishing of the hormonal effect. We did not study mating tests longer than 4 h

because, as aforementioned, after this interval the male is already sexually exhausted. The

results of this and the previous studies (Ågmo, 2007; Ventura-Aquino & Fernández-Guasti,

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2013b) support the notion that proceptivity may be considered as a motivational component

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that declines along continuous mating, most likely as a sign of a decreased in appetitive or

motivational aspects of sexual behavior. In addition, we have to take into consideration that

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proceptivity would be influenced by the male’s sexual activity that also decreased along 4h.

Additionally, it is possible that proceptivity remains present, even at very low levels, along

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all the time the gonadal hormones exert their action. If so, this behavioral parameter could
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not be a reliable indicator of sexual exhaustion in females.
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In another series of experiments, we analyzed the effect of sexual novelty in other

paradigms. We selected the sexual incentive motivation (SIM) because it evaluates

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approaching behaviors towards two sexual incentives presented simultaneously, with no

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physical contact (Ågmo et al., 2004); and the partner preference (PP) test, where was

possible physical and sexual contact with both incentives (Ventura-Aquino et al., 2016).
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After 1 hour of mating with a single male, females presented a higher SIM and spent more
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time with the unknown male during the PP test, independently if females regulate or not the
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time of mating.

So far, studies of the Coolidge effect in females are restricted to behavioral aspects.

For this reason, neuromediators involved are not yet evaluated. However, an approximation

by an in vivo microdialysis report made by James Pfaus and colleagues, found that sexually

receptive female rats showed an increase in DA efflux in the NA simply after exposing
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them to a male, that was maintained high along copulation (Pfaus et al., 1995). This

increase in DA is strikingly similar to that shown by males (Fiorino et al., 1997).

Additionally, the kinetics of DA efflux along the time of mating was similar between sexes

(Pfaus et al., 1995; Fiorino et al., 1997). However, the report by Pfaus did not evaluate the

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DA release after the presentation of an unknown male.

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Taking into consideration the aforementioned studies, sexual novelty influences

sexual behavior in females, denoting the Coolidge effect. However, this is still a research

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field that needs further exploration. Table 1 resumes some sexual satiety and Coolidge

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effect differences in females and males that must be considered.
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Some authors have proposed that the Coolidge effect is the result of the habituation-

dishabituation process to the same sexual stimulus (O'Donohue & Geer, 1985; Ågmo,
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2007), and that this process depends on stimulation variants such as type, duration and

variability, but also on the characteristics of the subject studied. These influences may be
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important in the case of human beings, because of the wide diversity of intrapersonal and
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extrapersonal influences on human sexual behavior. Therefore it is possible that the

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reproducibility of the Coolidge effect in non-human mammals is favored by controlling

laboratory conditions that reduce variability. But, in the case of humans sexual behavior is
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influenced by many biological, psychological and social variables that should be considered
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for the applicability of the sexual satiation and the Coolidge effect.

Some considerations about the Coolidge effect in humans

Sexual behavior in humans is modeled by factors that cannot be strictly controlled

under a laboratory environment. Some of them include individual and sociocultural

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connotations that undoubtedly are also influenced by the endocrine status (Atallah et al.,

2016; Brotto et al., 2016; Thomas & Thurston, 2016). For example, people with some

personality traits, develop different attitudes that relate with sexual aspects such as the

number of sexual partners, sexual activity frequency, sexual satisfaction, or engaging on

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risky sexual behaviors (Heaven et al., 2000; Hoyle et al., 2000; Allen & Desille, 2017).

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Although there are ethical limitations for the study of sexual satiation and the Coolidge

effect in humans, there is a considerable amount of reports that support the habituation and

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dishabituation to a sexual stimulus, with the general agreement that previous sexual

experience do not modify these phenomena (Heiman, 1977; Dawson et al., 2013).

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The habituation of sexual response in human males

The majority of reports in this topic have been conducted in men, have employed
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diverse sexually explicit content as stimuli, and have measured penile tumescence

employing devices such as mercury-in-rubber strain gauge or electromechanical strain

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gauge (O'Donohue & Geer, 1985; Dawson et al., 2013); and psychological sexual arousal,
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mainly evaluated by self-report scales, ranking the subjective sexual arousal (O'Donohue &

Geer, 1985; Kelley & Musialowski, 1986; Koukounas & Over, 1993; Morton & Gorzalka,
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2015). To produce habituation, there are different paradigms and stimuli types. For
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example, Howard and colleagues evaluated in men which were exposed 90 min per day to a
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room with diverse sexually explicit material during 15 consecutive days (Howard et al.,

1973). They measured sexual arousal using a strain gauge and the time spent attending the

material in each session. Disposal to continue in the study and sexual arousal declined over

days, concluding that the exposition to sexually explicit material leads to detriment on

interest and sexual arousal (Howard et al., 1973). Although the reliability of this report was
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questioned because they did not employ any statistical analysis and the strain gauge was not

calibrated, making measurements imprecise (O'Donohue & Geer, 1985).

O’Donohue et al., evaluated sexual arousal and subjective sexual arousal in men

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which were exposed to slides showing sexual content with two different intensities (high or

moderate), and two modalities, exposition to the same or different slides. Each presentation

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lasted one minute and there was a maximum of 27 presentations (O'Donohue & Geer,

1985). Independently of the intensity of stimuli, they found a decrease in the penile

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circumference along presentations that correlated with a decline in subjective ratings

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(O'Donohue & Geer, 1985). Later, the same research group studied sexual habituation in a
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long-term paradigm, employing auditory stimuli instead of visual (O'Donohue & Plaud,

1991). Men were exposed to a 2-minute audiotape about a sexually explicit situation for a
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total of six sessions, each one separated by 2-4 days. Each session consisted in 15

presentations of audiotapes. Some men were subjected half of the sessions to one audiotape
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and the rest of the tests to diverse audiotapes. They found a clear fall on penile tumescence
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with constant stimuli along sessions, whereas the men exposed to variations of stimuli did

not present the declined sexual response (O'Donohue & Plaud, 1991). The majority of
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studies that evaluated the sexual habituation in men have consistently found a detriment in
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penile tumescence accompanied by a decreased psychological sexual arousal after repeated

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exposition to the same stimulus (O'Donohue & Geer, 1985; O'Donohue & Plaud, 1991;

Koukounas & Over, 1993; Dawson et al., 2013; Morton & Gorzalka, 2015). However, in

all the aforementioned reports, it was omitted the study of reward that usually occurs after

being exposed to sexual explicit stimuli, on the habituation process. In this regard, Schaefer

and colleagues (1977) evaluated if reward, immediately after the stimulus, modified the
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sexual habituation pattern in men (Schaefer & Colgan, 1977). They employed extracts of

the book “Sexus” written by Henry Miller, which contents erotic scenes. Protocol consisted

on four groups that read the same fragment of the text during six times, or read six different

extracts (Schaefer & Colgan, 1977). One group from each condition masturbated after

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every session, whereas others did not masturbate. All groups presented a decline in the

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erection response after repeated exposition, but the decrease was less sharp in the group

that was allowed to masturbate, concluding that reward delays the habituation process

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(Schaefer & Colgan, 1977).

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Considering the aforementioned studies, there is strong evidence that indicates the
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habituation of sexual response in men, both in sexual arousal, evaluated by penile

tumescence, and subjective sexual arousal. The habituation process could be ameliorated by
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sexual reward. In women, however, not such a clear consensus has been established (vide

infra).
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The sexual response habituation in the human female

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Genital arousal in women is measured by vaginal plethysmography and subjective

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arousal by a self-reported scale. Regarding the habituation of the women's sexual response,

there is a smaller number of reports that show inconsistent results, as compared with those
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involving men. For example, Ingrid Meuwinssen and colleagues (1990) evaluated sexual
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arousal in women who watched the same erotic film or engaged in a sexual fantasy for 18

times (Meuwissen & Over, 1990). After initial presentations, the stimulus was changed for

a novel film or fantasy twice. They found a typical habituation-dishabituation pattern in

genital and subjective arousal. Other research group also found that repeated exposition to

the same erotic film or the same sexual fantasy decreased genital and subjective sexual
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arousal, similarly than in men (Dawson et al., 2013). However, there are some reports that

contrast with these observations. For example, a study employing images with sexual

content did not find a decline in genital arousal in women over ten presentations of the

same image, failing to denote habituation to the same stimuli; however, at the eleventh trial,

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the authors presented a novel image and found an increase in genital arousal (Laan &

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Everaerd, 1995). They explained the lack of habituation due to a floor’s effect, because the

basal levels of genital arousal remained low after the first three presentations. They also

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observed lower basal levels of sexual arousal in women than in men. Finally, they

considered that pictures, instead of films, could have induced lower arousal rates (Laan &

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Everaerd, 1995). Thereby, in a second experiment, they evaluated films (instead of slides)
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as stimuli. Although they found higher basal levels of genital arousal, women exposed to

the same film did not show a decrease in this response over 21 expositions, although the
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presentation of a novel film induced a marked increase in genital arousal (Laan & Everaerd,
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1995). These results suggested that the women’s sexual response is more stable to the same
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stimuli, even though sexual novelty can increase it.

Explanations for the discrepancies between the results in women could imply
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methodological aspects such as the hormonal stage or refining apparatus measurements.

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However, there is a recent notion regarding sexual arousal that is worth mentioning. The
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pattern of genital arousal in women is category-nonspecific, e.g. genital arousal, measured

by vaginal plethysmography, is activated to a wide modality of sexual stimuli, including

those that coincide or not with the woman’s specific sexual preferences, desires or interests

(Chivers & Bailey, 2005; Suschinsky et al., 2009; Chivers, 2017); contrasting with

women’s subjective arousal, that is category-specific.

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There are a few of reports that compare habituation of sexual response in both

sexes, reporting differences in habituation patterns between men and women. For example,

Kathryn Kelley and colleagues (1986) evaluated sexual arousal to the same film repeated

four times; in the fifth presentation, they evaluated two conditions: the same actors making

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different sexual activities, or different players making the same sexual acts. As others, they

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found a decreased sexual response and interest along the four presentations, but in the last

evaluation, men showed sexual arousal and interest to actors’ changing, although they

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performed similar sexual activities; whereas women were more sexually aroused and

interested to different sexual acts although acted by the same performers (Kelley &

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Musialowski, 1986). In other report, Samantha Dawson and colleagues evaluated
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habituation and dishabituation patterns in men and women. Participants were exposed to 60

sec of erotic film nine times, following by two presentations of a different film (novel) and
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a final presentation of the initial erotic movie (Dawson et al., 2013). Along the experiment,
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they measured sexual arousal by strain gauge, in the case of males, and vaginal
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photoplethysmography, for women. They concluded that habituation-dishabituation

patterns are similar in men and women, i.e. for both sexes, sexual arousal declined from the
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basal to the ninth exposition, this response increased with the novel erotic film and again

declined with the presentation of the original film (Dawson et al., 2013).
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As aforementioned this research field is growing and would be relevant to elucidate

differences between the female and male sexual response to design protocols more

appropriated for each sex.

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Conclusions
In both, males and females, there is a decline of sexual arousal after repeated

exposition to the same sexual stimulus. This effect seems to be general to the whole range

of species studied, including humans, although the results in women have to be further

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explored. Sexual novelty increases motivational aspects of sexual behavior in males,

evidenced by the Coolidge effect. In females, including women, the expression of that

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effect is related to other factors that affect sexual behavior, such as the period of the

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endocrine cycle. These peculiarities should be considered in future studies evaluating the

Coolidge effect in males and females, including human beings. The molecular mechanisms

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underlying sexual satiety are poorly understood; recent experimental data in rats suggest
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that DA may play a similar role in both sexes. Those mechanisms mediating the Coolidge

effect are largely unknown but most likely involve also mediators that participate in the
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regulation of motivation, although memory and novelty processes have also to be

considered. In humans, particularly in women, the large influence of psychological and

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social features affecting sexual responses have to be added to the variables that may affect
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habituation and dishabituation to a given sexual partner.

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Acknowledgements

The authors wish to thank M.Sc. Rebeca Reyes-Serrano and Mrs. Blanca Gómez Quintanar
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for technical assistance. We are also thankful to CONACyT for granting fellowship number
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243413 to EV-A.
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Males Females References

(Dewsbury, 1981; Lisk &

Numerous reports in many Baron, 1982; Steiger et al.,
A few reports limited to hamsters
mammalian and non- 2008; Tlachi-López et al.,

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and rats. 2012; Ventura-Aquino et
mammalian species
al., 2016)

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Sexual behavior is restricted to
Evaluating the spontaneous
the duration of the ovarian
recovery of sexual behavior (Romano-Torres et al.,
hormonal levels during the
after sexual satiety is possible 2007; Blaustein, 2009; He

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proestrous phase of the estrous et al., 2013)
because of the stable
cycle or by exogenous
testicular hormones levels
supplementation.

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There are different sexual satiety (Lisk & Baron, 1982;
Sexual satiety criteria involve Rodriguez-Manzo, 1999;
criteria, depending on the report
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the absence of sexual Ågmo, 2007; Ventura-
and species, which would not Aquino & Fernández-
behavior, mainly observed in
include a complete inhibition of Guasti, 2013b; Ventura-
mounting behavior.
sexual behavior. Aquino et al., 2016)
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Sexual motivation renewal –by

Sexual motivation renewal – novel stimuli- is possible in
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(Ågmo et al., 2004; Ågmo,

by novel stimuli- is possible in sexually exhausted and non- 2007; Ventura-Aquino et
sexually exhausted and non- exhausted females, even there is a al., 2016)
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exhausted males. different sexual satiety criterion

than that used in males.

Male human sexual response In women, there is not a

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(O'Donohue & Geer, 1985;

consistently shows habituation consensus about the habituation O'Donohue & Plaud, 1991;
and dishabituation patterns pattern but the presentation of Koukounas & Over, 1993;
that permits to infer the novel stimuli increases genital Suschinsky & Lalumière,
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Coolidge effect in men. arousal. 2011; Dawson et al., 2013)

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Table 1. Differences between males and females in sexual satiety and the Coolidge effect.
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Figure legends

Figure 1. Temporality of sexual satiety and the Coolidge effect in the male rat. After around
150 minutes of continuous mating with a single female, the male becomes sexually satiated
and does not achieve an ejaculation after 90 minutes. If a new female is immediately
presented, the male resumes mating. Twenty-four hours after, sexual exhaustion is

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maximal; it cannot be reversed by an unknown female but can be pharmacologically
reversed. After 15 days, sexual activity in males is fully restored.

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Figure 2. Proceptive behaviors (number per minute) along 4 h of paced and non-paced
mating in the female rat in natural proestrus. Each bar represents the frequency of behaviors

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during an ejaculatory series (encompassing all events from the first intromission to
ejaculation). RM-Two way ANOVA (ejaculatory series, mating condition). ES 1: the first
ejaculatory series, ES 2: the second ejaculatory series, PUES: the penultimate ejaculatory
series, LES: the last ejaculatory series. *p<0.05, **p<0.01, ***p<0.001, different from ES

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1; #p<0.05; ##p>0.01, ###p<0.001, different from Non-paced mating group. Tukey post
hoc test.
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Sexual satiety
Male mating with a Until Progressive reversion of sexual satiety

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single female presenting 90
≈150 min min with no 24 h 14 days Full

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additional restoration
≈ 7 ejaculations ejaculation

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Reversion by
Novel female pharmacological

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agents
Coolidge effect

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Figure 1. Temporality of sexual satiety and the Coolidge effect in the male rat. After around 150 minutes of continuous mating with a
single female, the male becomes sexually satiated and does not achieve an ejaculation after 90 minutes. If a new female is immediately
presented, the male resumes mating. Twenty-four hours after, sexual exhaustion is maximal; it cannot be reversed by an unknown
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female but can be pharmacologically reversed. After 15 days, sexual activity in males is fully restored.
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Figure 2. Proceptive behaviors (number per minute) along 4 h of paced and non-paced mating in the female rat in natural proestrus. Each
bar represents the frequency of behaviors during an ejaculatory series (encompassing all events from the first intromission to ejaculation).
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RM-Two way ANOVA (ejaculatory series, mating condition). ES 1: the first ejaculatory series, ES 2: the second ejaculatory series, PUES:
the penultimate ejaculatory series, LES: the last ejaculatory series. *p<0.05, **p<0.01, ***p<0.001, different from ES 1; #p<0.05; ##p>0.01,
###p<0.001, different from Non-paced mating group. Tukey post hoc test.
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Highlights

The Coolidge effect is the sexual motivation renewal due to sexual novelty.

There are several reports in males, mostly related to sexual satiety (an inhibition after continuous
mating) which involves various neurobiological changes.

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Studies in females are scarce, but with growing evidence indicating that sexual novelty also
influences sexual motivation.

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Sexual novelty modifies sexual behavior in men and women, possibly in a sex-specific manner.

The effects of sexual novelty and motivation differ between sexes because of the differences in

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mating behavior features.

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