Sex Differences in Sexual Motivation in Humans and Other Mammals: The Role of Conscious and Unconscious Processes.

In self-report questionnaires, men report higher scores than women on variables such as desire for sex, frequency of sexual thoughts, number of sex partners, etc. Based on this, men are considered to have a higher level of sexual motivation than women. However, retrospective self-reports may be unsuitable for estimations of the inherent level of sexual motivation. We review data on automatic (unconsciously controlled) responses and measures of implicit motivation during exposure to sexual stimuli. These responses and measures are inaccessible to willful manipulations and make it possible to determine whether the sex difference in answers to questionnaires is replicated when volitional response manipulations are unlikely. We complement the human data with observations from some rodent and non-human primate species. The attentional resources allotted to stimuli with sexual relevance as well as genital responses to such stimuli are similar in men and women. Measures of implicit motivation also fail to detect any sex difference. Finally, the frequency of masturbation is superior in female infants before the age at which social expectations begin to determine behavior. Neither in rodents nor in non-human primates is there any clear-cut evidence for sex differences in motivation. It seems that males and females are similar with regard to the intensity of sexual motivation. The responses to questionnaires may be affected by social learning of sexual scripts and/or the inferior quality of sexual experiences in women, among other things.

Androgen receptors and sociosexual behaviors in mammals: The limits of generalization.

Circulating testosterone is easily aromatized to estradiol and reduced to dihydrotestosterone in target tissues and elsewhere in the body. Thus, the actions of testosterone can be mediated either by the estrogen receptors, the androgen receptor or by simultaneous action at both receptors. To determine the role of androgens acting at the androgen receptor, we need to eliminate actions at the estrogen receptors. Alternatively, actions at the androgen receptor itself can be eliminated. In the present review, I will analyze the specific role of androgen receptors in male and female sexual behavior as well as in aggression. Some comments about androgen receptors and social recognition are also made. It will be shown that there are important differences between species, even between strains within a species, concerning the actions of the androgen receptor on the behaviors mentioned. This fact makes generalizations from one species to another or from one strain to another very risky. The existence of important species differences is often ignored, leading to many misunderstandings and much confusion.

Sexual Incentive Motivation and Sexual Behavior: The Role of Consent.

The generalized social concern with sexual harassment and nonconsensual sex makes it imperative to incorporate notions of consent in any analysis of human sexual interactions. Such interactions follow an ordered sequence of events, starting with the perception of a sexual incentive, followed by an approach to it, genital interaction, and eventually orgasm. Consent from the partner is needed at every stage. At some points in this chain of events, the individuals involved make cognitive evaluations of the context and predictions of the likelihood for obtaining consent for proceeding to the next phase. Processes such as communication of consent or lack thereof, sexual decision making, and interpretation of cues emitted by the partner are decisive. Increased sexual motivation may influence these processes. However, available data make it possible to ascertain that enhanced motivation has no, or at most minor, effects, thereby invalidating the old assumption that heightened sexual motivation leads to impaired control.

The elusive concept of sexual motivation: can it be anchored in the nervous system?

Sexual motivation is an abstract concept referring to the mechanisms determining the responsivity to sexually relevant stimuli. This responsivity determines the likelihood of producing a sexual response and the intensity of that response. Both responsivity to stimuli and the likelihood of making a response as well as the intensity of response are characteristics of an individual. Therefore, we need to assume that the concept of sexual motivation materializes in physiological mechanisms within the individual. The aim of the present communication is to analyze the requisites for the endeavor to materialize sexual motivation. The first requisite is to provide an operational definition, making the concept quantifiable. We show that parameters of copulatory behavior are inappropriate. We argue that the intensity of sexual approach behaviors provides the best estimate of sexual motivation in non-human animals, whereas the magnitude of genital responses is an exquisite indicator of human sexual motivation. Having assured how to quantify sexual motivation, we can then proceed to the search for physiological or neurobiological underpinnings. In fact, sexual motivation only manifests itself in animals exposed to appropriate amounts of gonadal hormones. In female rats, the estrogen receptor α in the ventrolateral part of the ventromedial nucleus of the hypothalamus is necessary for the expression of sexual approach behaviors. In male rats, androgen receptors within the medial preoptic area are crucial. Thus, in rats sexual motivation can be localized to specific brain structures, and even to specific cells within these structures. In humans, it is not even known if sexual motivation is materialized in the brain or in peripheral structures. Substantial efforts have been made to determine the relationship between the activity of neurotransmitters and the intensity of sexual motivation, particularly in rodents. The results of this effort have been meager. Likewise, efforts of finding drugs to stimulate sexual motivation, particularly in women complaining of low sexual desire, have produced dismal results. In sum, it appears that the abstract concept of sexual motivation can be reliably quantified, and the neurobiological bases can be described in non-human animals. In humans, objective quantification is feasible, but the neurobiological substrate remains enigmatic.

Seminatural environments for rodent behavioral testing: a representative design improving animal welfare and enhancing replicability.

The low replicability of scientific studies has become an important issue. One possible cause is low representativeness of the experimental design employed. Already in the 1950's, Egon Brunswick pointed out that experimental setups ideally should be based on a random sample of stimuli from the subjects' natural environment or at least include basic features of that environment. Only experimental designs satisfying this criterion, representative designs in Brunswikian terminology, can produce results generalizable beyond the procedure used and to situations outside the laboratory. Such external validity is crucial in preclinical drug studies, for example, and should be important for replicability in general. Popular experimental setups in rodent research on non-human animals, like the tail suspension test or the Geller-Seifter procedure, do not correspond to contexts likely to be encountered in the animals' habitat. Consequently, results obtained in this kind of procedures can be generalized neither to other procedures nor to contexts outside the laboratory. Furthermore, many traditional procedures are incompatible with current notions of animal welfare. An approximation to the natural social and physical context can be provided in the laboratory, in the form of a seminatural environment. In addition to satisfy the basic demands for a representative design, such environments offer a far higher level of animal welfare than the typical small cages. This perspective article will briefly discuss the basic principles of the generalizability of experimental results, the virtues of representative designs and the coincidence of enhanced scientific quality and animal welfare provided by this kind of design.

The Sexual Incentive Motivation Model and Its Clinical Applications.

Sexual motivation (desire) requires the simultaneous presence of an active central motive state and a stimulus with sexual significance. Once activated, sexual motivation leads to visceral responses and approach behaviors directed toward the emitter of the sexual stimulus. In humans, such behaviors follow cognitive evaluation of the context, including predictions of the approached individual's response. After successful approach and establishment of physical contact, manifest sexual activities may be initiated. Sexual interaction is associated with and followed by a state of positive affect in most animals, whereas aversive consequences may be experienced by humans. The affective reactions may become associated with stimuli present during sexual interaction, and these stimuli may thereby alter their incentive properties. Here we show how the incentive motivation model can be used to explain the origins and possible treatments of sexual dysfunctions, notably disorders of desire. We propose that associations formed between negative outcomes of sexual interaction and the salient stimuli, for example, the partner, underlies hypoactive desire disorder. Highly positive outcomes of sexual interaction enhance the incentive value of the stimuli present, and eventually lead to hyperactive sexual desire. Treatments aim to alter the impact of sexual incentives, mainly by modifying cognitive processes.

Neuroendocrinology of sexual behavior.

One of the consequences of sexual behavior is reproduction. Thus, this behavior is essential for the survival of the species. However, the individual engaged in sexual behavior is rarely aware of its reproductive consequences. In fact, the human is probably the only species in which sexual acts may be performed with the explicit purpose of reproduction. Most human sexual activities as well as sex in other animals is performed with the aim of obtaining a state of positive affect. This makes sexual behavior important for wellbeing as well as for reproduction. It is not surprising, then, that sexual health has become an increasingly important issue, and that knowledge of the basic mechanisms controlling that behavior are urgently needed. The endocrine control of sexual behavior has been extensively studied, and although it is established that gonadal hormones are necessary, some controversy still exists concerning which hormone does what in which species. The brain areas necessary for sexual behavior have been determined in almost all vertebrates except the human. The medial preoptic area is crucial in males of all non-human vertebrates, whereas the ventromedial nucleus of the hypothalamus is important in females. Modulatory functions have been ascribed to several other brain areas.

Sexual incentive motivation, sexual behavior, and general arousal: Do rats and humans tell the same story?

Sexual incentive stimuli activate sexual motivation and heighten the level of general arousal. The sexual motive may induce the individual to approach the incentive, and eventually to initiate sexual acts. Both approach and the ensuing copulatory interaction further enhance general arousal. We present data from rodents and humans in support of these assertions. We then suggest that orgasm is experienced when the combined level of excitation surpasses a threshold. In order to analyze the neurobiological bases of sexual motivation, we employ the concept of a central motive state. We then discuss the mechanisms involved in the long- and short-term control of that state as well as those mediating the momentaneous actions of sexual incentive stimuli. This leads to an analysis of the neurobiology behind the interindividual differences in responsivity of the sexual central motive state. Knowledge is still fragmentary, and many contradictory observations have been made. Nevertheless, we conclude that the basic mechanisms of sexual motivation and the role of general arousal are similar in rodents and humans.

Sexual Incentive Motivation and Copulatory Behavior in Male Rats Treated With the Adrenergic α2-Adrenoceptor Agonists Tasipimidine and Fadolmidine: Implications for Treatment of Premature Ejaculation.

BACKGROUND: Premature ejaculation is the most common sexual dysfunction in young men, and it often leads to reduced relationship satisfaction and quality of life. AIM: To determine the role of central and peripheral α2-adrenoceptors in the control of ejaculation and sexual incentive motivation in rats. METHODS: Sexual incentive motivation was studied in a large arena in which a male subject could choose between approaching and remaining close to a sexually receptive female or another male. Sexual behavior was studied in standard observation cages in which a male was allowed to freely interact with a receptive female for 30 minutes. Two highly selective agonists at the α2-adrenoceptors, tasipimidine and fadolmidine, were administered before the tests. Low peripheral doses of fadolmidine have been reported to have effects mainly outside of the central nervous system, whereas at large doses also the central effects are evident. OUTCOMES: The time spent close to the receptive female in relation to the time spent with the male and measures of ambulatory activity were obtained from the test for sexual incentive motivation, while the habitual parameters of sexual behavior were recorded with the copulation test. RESULTS: Tasipimidine prolonged ejaculation latency and the interintromission interval at the dose of 200 µg/kg when data from fast-ejaculating rats were used. No other sexual parameter was modified. A dose of 100 µg/kg was ineffective. There was no consistent effect on sexual incentive motivation, although modest sedation was observed. Fadolmidine, a drug that does not easily penetrate the blood-brain barrier, had no effect on sexual incentive motivation at any of the doses used (3, 30, and 100 µg/kg). The largest dose had clear sedative effects. The lower doses had no systematic effect on sexual behavior, not even when only fast or very fast ejaculating males were analyzed. CLINICAL TRANSLATION: The findings are relevant to the search for treatments for premature ejaculation that are specific enough to selectively delay ejaculation. STRENGTHS & LIMITATIONS: The procedures used here are standard in the field and yield the most reliable data. Whether the effects observed in male rats are directly transferrable to men can only be determined through clinical studies. CONCLUSION: The observation that drugs acting at central but not peripheral α2-adrenoceptors prolong ejaculation latency without affecting any other parameter of sexual behavior or sexual incentive motivation suggests that this kind of drug may be suitable for treating premature ejaculation. Jyrki L., Elisa V.-A., Xi C., et al. Sexual Incentive Motivation and Copulatory Behavior in Male Rats Treated With the Adrenergic α2-Adrenoceptor Agonists Tasipimidine and Fadolmidine: Implications for Treatment of Premature Ejaculation. J Sex Med 2021;18:1677-1689.

Sexual incentive motivation and male and female copulatory behavior in female rats given androgen from postnatal day 20.

Masculinization and feminization of rat sexual behavior has been supposed to occur during a short postnatal period. However, much data have made it evident that these processes may continue until adolescence. In the present study, we evaluated whether androgen treatment of females from postnatal day 20 and onwards could alter sexual motivation and behavior in a male direction. Juveniles were ovariectomized on day 20 and concurrently implanted with Silastic capsules containing either testosterone or dihydrotestosterone. Controls were implanted with an empty capsule. Tests for sexual incentive motivation and male sexual behavior were performed every fifth day when the females were between 50 and 75 days of age. At day 80, a test for female sexual behavior was performed. Females treated with testosterone approached a female sexual incentive far more than a male incentive, showing that sexual motivation had been changed in a male-like direction. Dihydrotestosterone had a similar, albeit smaller, effect. Females implanted with an empty capsule approached both incentives equally. Testosterone produced a high level of mounting behavior, whereas intromission-like behavioral patterns were rare and ejaculation-like behavior was absent. In the test for female sexual behavior, the testosterone-treated animals displayed a relatively high lordosis quotient, far above that displayed in females implanted with dihydrotestosterone or an empty capsule. It is concluded that treatment with an aromatizable androgen during the peripubertal-adolescent period masculinizes sexual motivation and partly sexual behavior. A non-aromatizable androgen weakly masculinize sexual motivation without enhancing male sexual behavior. It appears that simultaneous actions on androgen and estrogen receptors are needed for significant masculinization during the period studied here. Since the testosterone-treated females displayed lordosis, sexual behavior was not defeminized. In sum, these results suggest that sexual differentiation continues well into the peripubertal and adolescent periods.

Rat ultrasonic vocalizations and novelty-induced social and non-social investigation behavior in a seminatural environment.

Although rats are known to emit ultrasonic vocalizations (USVs), it remains unclear whether these calls serve an auditory communication purpose. For USVs to be part of communication, the vocal signals will need to be a transfer of information between two or more conspecifics, and with the possibility to induce changes in the behavior of the recipient. Therefore, the aim of our study was to investigate the role of USVs in adult rats' social and non-social investigation strategies when introduced into a large novel environment with unfamiliar conspecifics. We quantified a wide range of social and non-social behaviors in the seminatural environment, which could be affected by subtle signals, including USVs. We found that during the first hour in the seminatural environment the ability to vocalize did not affect how quickly adult rats met each other, their overall social investigation behavior, their passive social behavior nor their aggressive behavior. Furthermore, the non-social exploratory behaviors and behaviors reflecting anxiety/stress-like states were also unaffected. These results demonstrated that a disability to vocalize did not result in significant disadvantages (or changes) compared to intact conspecifics regarding social and non-social behaviors. This suggests that other (multi)sensory cues are more relevant in social interactions than USVs.

Male and female immediate fear reaction to white noise in a semi-natural environment: A detailed behavioural analysis of the role of sex and oestrogen receptors.

In classical rodent anxiety models, females usually display lower anxiety than males, whereas anxiety disorders are more prevalent in women. Perhaps this contradiction is caused by the use of behavioural models with low external validity. Therefore, we analysed immediate reactions to a sudden 90-dB white noise in a semi-natural environment. We observed mixed-sex groups of rats for the 60 seconds preceding noise onset and the first 60 seconds of exposure. White noise elicited fear-specific behaviours hiding alone and huddling. It also increased exploratory and ambulatory behaviours, although only in the burrow zone farthest from the open area. Thus, in a semi-natural environment, white noise enhanced motor activity as a product of fear-induced general arousal. Then, we compared male and female sexual, social, exploratory and anxiety-related behaviour, and found little sex difference. This absence of behavioural effect, also observed in other studies, might be a result of our study design, a familiar environment with an ecologically relevant social context. Fear and anxiety responses are modulated by oestrogens through the activation of oestrogen receptors α and ß. Thus, in a third part of out study, we analysed how treatment with either oil, oestradiol benzoate (EB), an agonist to the oestrogen receptor α (propylpyrazoletriol [PPT]) or ß (diarylpropionitrile [DPN]) influenced female behaviour. The effect of treatment was limited, both EB and PPT stimulated motor activity in the open area before white noise, probably because of sexual activity. PPT increased the probability of fleeing from the noise, and decreased the latency to do so, which is consistent with a pattern of anxiogenic properties found in previous studies. Contrary to reports in classical procedures, we failed to detect any effect of DPN on immediate fear reactions in a semi-natural environment.

Pubertal stress decreases sexual motivation and supresses the relation between cerebral theta rhythms and testosterone levels in adult male rats.

This study evaluated the effect of stress during puberty on sexual motivation and the correlation between serum testosterone levels (T) and the absolute power of the theta electroencephalographic rhythms, recorded in the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) of adult male rats. Thirty males of the stressed group (SG, housed 1 per cage from days 25-50) and 30 controls (CG, housed 5 per cage), were tested in copulatory interactions at 90 days of age. The above mentioned physiological parameters were obtained during the awake-quiet state in a sub-group without sexual motivation (WSM, n = 15, stimulated with a nonreceptive female) and a sub-group with sexual motivation (SM, n = 15, stimulated with a receptive-female). Pearson correlations (r) between these parameters were calculated for each sub-group and brain structure and then compared between sub-groups. SG presented higher mount and intromission latencies than CG. While CG-WSM showed a positive r between T levels and theta band (0.23-0.59), those CG-SM presented a negative r (-0.23 to -0.67). An r that tended towards zero (-0.31 to 0.29) was obtained in both stressed sub-groups. This study shows that pubertal stress suppresses the relation between serum T levels and theta rhythms in the mPFC and BLA in adult male rats. This is one of the first studies evaluating the association between these two physiological parameters specifically in the context of sexual motivation; thus increasing our understanding of the effect of pubertal stress on prefrontal-amygdaline functioning during the sexually-motivated state in male rats.

Rapid changes in sociosexual behaviors around transition to and from behavioral estrus, in female rats housed in a seminatural environment.

Gonadally intact female rats display sexual behaviors only during a portion of the estrus cycle. In standard experimental setups, the on- and offset of sexual behavior is gradual. However, in naturalistic settings, it is almost instantaneous. We assessed the changes in sociosexual behaviors at the beginning and end of behavioral estrus in ovariectomized females treated with ovarian hormones. Rats were housed in a seminatural environment, in groups of three males and four females. We scored female and male behavior during the 8 min preceding and following the first and last lordosis of behavioral estrus. Immediately before the first lordosis, there was a sharp increase in female paracopulatory behaviors whereas the end of estrus was marked by a sudden decrease in these behaviors. There was no systematic change in other female behavior patterns. These data suggest that the display of female paracopulatory behaviors plays a key role. Both during transition into and out of behavioral estrus, most behavioral changes occurred within one minute. The rapid changes must be unrelated to ovarian hormone fluctuations in these ovariectomized females. Perhaps they can be explained in terms of hormone-induced, dynamic (chaotic) changes in the function of critical structures within the brain.

Modeling Human Sexual Motivation in Rodents: Some Caveats.

Sexual behavior is activated by motivation. An overwhelming majority of experimental studies of the intricacies of sexual motivation has been performed in rodents, most of them in rats. Sometimes it is desirable to generalize results obtained in this species to other species, particularly the human. It is hoped that studies of the neurobiology of rodent sexual behavior may shed light on the central nervous mechanisms operating in the human, and the search for efficient pharmacological treatments of human sexual dysfunctions relies partly on studies performed in rodents. Then the issue of generalizability of the rodent data to the human becomes crucial. We emphasize the importance of distinguishing between copulatory acts, behavior involving the genitals, and the preceding event, the establishment of physical contact with a potential mate. Comparisons between the structure of copulatory behavior in rats and humans show abysmal differences, but there may be some similarity in the underlying mechanisms. The endocrine control of sex behavior is shortly mentioned, and we also compare the effects of the few drugs known to affect both rodent and human copulatory behavior. The stimuli activating sexual motivation, often called desire in the human literature, are examined, and the sexual approach behaviors in rats and humans are compared. There is a striking similarity between these species in how these behaviors respond to drugs. It is then shown that the intensity of sexual approach is unrelated to the intensity of copulatory behavior. Even though the approach is a requisite for copulation, an activity that requires at least two individuals in close physical contact, these two aspects of sexuality do not covary. This is similar to the role of the testosterone in men and male rats: although the hormone is needed for sex behavior, there is no correlation between serum testosterone concentration and the intensity of copulation. It is also pointed out that human sexual behavior is mostly determined by social conventions, whereas this is not the case in rats and other rodents. It is concluded that some observations in rats can be generalized to the human, but extreme caution must be exercised.

Estrogen receptors α and ß in the central amygdala and the ventromedial nucleus of the hypothalamus: Sociosexual behaviors, fear and arousal in female rats during emotionally challenging events.

Estrogens receptors (ER) are involved in several sociosexual behaviors and fear responses. In particular, the ERα is important for sexual behaviors, whereas ERß modulates anxiolytic responses. Using shRNA directed either against the ERα or the ERß RNAs (or containing luciferase control) encoded within an adeno-associated viral vector, we silenced these receptors in the ventromedial nucleus of the hypothalamus (VMN) and the central amygdala (CeA). We exposed ovariectomized female rats, sequentially treated with estradiol benzoate and progesterone, to five stimuli, previously reported to elicit positive and negative affect. The subjects were housed in groups of 4 females and 3 males in a seminatural environment for several days before hormone treatment. We analyzed the frequency of a large number of behavior patterns. In addition, we performed analyses of co-occurrence in order to detect changes in the structure of behavior after infusion of the vectors. Silencing the ERα in the VMN disrupted lordosis and showed some anxiolytic properties in aversive situations, whereas silencing of the ERß in this structure had no effect. This was also the case after silencing the ERα in the CeA. Silencing of the ERß in this structure increased risk assessment, an expression of anxiety, and increased olfactory exploration of the environment. We hypothesize that the ERß in the CeA has an important role in the well-established anxiolytic effects of estrogens, and that it may modulate arousal level. Furthermore, it seems that the ERα in the VMN is anxiogenic in aversive or threatening situations, in agreement with other studies.

Responses to positive and aversive stimuli in estrous female rats housed in a seminatural environment: Effects of yohimbine and chlordiazepoxide.

The behavioral effects of putative anxiolytic and anxiogenic drugs are usually evaluated in highly standardized tests. Here, we determined the effects of such drugs in rats housed in mixed sex groups in a seminatural environment. Sexually receptive female Wistar rats were treated with either the anxiolytic drug chlordiazepoxide (2 mg/kg), the anxiogenic drug yohimbine (1 mg/kg), or saline (1 ml/kg). Different emotional challenges eliciting purportedly positive affect (lavender odor, Mozart's music, chocolate flavored food) or negative affect (white noise, fox odor) were then introduced into the seminatural environment. A co-occurrence analysis revealed that music was rather aversive to the rats, as were white noise and fox odor. Lavender and chocolate exposure decreased classical indicators of fear. White noise suppressed sexual behaviors and caused avoidance of the open area. Yohimbine increased sexual receptivity during lavender exposure, decreased the latency to flee the white noise, and increased self-grooming regardless of the emotional challenge. Chlordiazepoxide was effective only during exposure to white noise, and increased the frequency of hiding alone. The modest effects of the drugs in the seminatural environment may be the result of social buffering and rats experiencing a high degree of controllability over their environment.

Behavioral response is absent under the mating competition in rats (Rattus norvegicus).

Sexually receptive female rats normally copulate with several males during estrus, and multiple paternity is common. Sperm competition is therefore likely to occur. One response to competitive mating is to enhance sperm output per ejaculation and another is to augment the number of ejaculations. The latter alternative requires more intense copulatory behavior. In studies in a seminatural environment we observed that male rats did not modify their behavior according to the intensity of competition, whereas observations from standard observation cages suggested that they do so. In order to further evaluate the potential response to competitive mating, we observed male rats copulating in a pair situation, i.e. one male and one female, and in a situation where three males simultaneously copulated with one female. In addition to sexual behavior, social interactions were quantified. It was found that the males in the multiple male condition prolonged mount and intromission latencies, and displayed a reduced number of mounts. There was no change in the number of preejaculatory intromissions or the ejaculation latency. The multiple mating did not affect non-sexual interactions with the female, whereas the female displayed more nose-offs and rejections when copulating with three males. It is concluded that mating competition does alter the initiation of copulation in the male rat, whereas copulatory behavior, i.e. intromission and ejaculation, remains unchanged.

The Role of Estrogen Receptor ß (ERß) in the Establishment of Hierarchical Social Relationships in Male Mice.

Acquisition of social dominance is important for social species including mice, for preferential access to foods and mates. Male mice establish social rank through agonistic behaviors, which are regulated by gonadal steroid hormone, testosterone, as its original form and aromatized form. It is well known that estrogen receptors (ERs), particularly ER α (ERα), mediate effects of aromatized testosterone, i.e., 17ß-estradiol, but precise role played by ER ß (ERß) is still unclear. In the present study, we investigated effects of ERß gene disruption on social rank establishment in male mice. Adult male ERß knockout (ßERKO) mice and their wild type (WT) littermates were paired based on genotype- and weight-matched manner and tested against each other repeatedly during 7 days experimental period. They underwent 4 trials of social interaction test in neutral cage (homogeneous set test) every other day. Along repeated trials, WT but not ßERKO pairs showed a gradual increase of agonistic behaviors including aggression and tail rattling, and a gradual decrease of latency to social rank determination in tube test conducted after each trial of the social interaction test. Analysis of behavioral transition further suggested that WT winners in the tube test showed one-sided aggression during social interaction test suggesting WT pairs went through a process of social rank establishment. On the other hand, a dominant-subordinate relationship in ßERKO pairs was not as apparent as that in WT pairs. Moreover, ßERKO mice showed lower levels of aggressive behavior than WT mice in social interaction tests. These findings collectively suggest that ERß may play a significant role in the establishment and maintenance of hierarchical social relationships among male mice.

Behavioral responses to emotional challenges in female rats living in a seminatural environment: The role of estrogen receptors.

Estrogen receptors (ERs) are involved in sexual as well as non-sexual behaviors. In the present study we assessed the effects of stimuli inducing positive or negative affect on sociosexual, exploratory and fear-related behaviors of female rats housed in groups (4 females, 3 males) in a seminatural environment. Ovariectomized females were treated with oil, 17ß­estradiol benzoate (EB, 18 µg/kg), the ERα agonist propylpyrazoletriol (PPT), or the ERß agonist diarylpropionitrile (DPN) (both 2 × 10 mg/rat). On the test day, the females were exposed to a sequence of events consisting of lavender odor, Mozart's Sonata for Two Pianos K448, chocolate pellets, white noise and fox odor (2,3,5­Trimethyl­3­thiazoline, TMT). All these events are known to induce positive or negative affect. Behavior was carefully observed from the video record. White noise suppressed sexual behaviors and reduced the time spent in the open area of the environment. TMT had no consistent effect whereas exposure to music caused avoidance of the open area. Exposure to chocolate increased exploratory and social behavior. Lavender odor enhanced exploratory behavior. PPT and EB stimulated sexual behaviors, whereas DPN was ineffective. Co-occurrence analyses of the sequence of behavioral patterns revealed that PPT and EB consistently belonged to clusters different from oil and DPN, whereas DPN was separate from oil only under fear-inducing experimental conditions. These data, from a procedure with external validity, confirm that the ERα is crucial for sexual behaviors, that these behaviors are reduced under stressful conditions, and that the ERß may have some role in fear-related behaviors.