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Synthetic progestins such as medroxyprogesterone acetate (MPA) are used widely in the treatment of male sex offenders. In male cynomolgus monkeys (Macaca fascicularis) treated with testosterone (T), both MPA and progesterone (P) had comparable inhibitory effects on male sexual motivation and behavior. To determine if P, like MPA, decreases endogenous T levels, plasma T and P levels were analyzed in weekly blood samples (N=186) from eight intact males, each paired with a sexually receptive female before, during, and after treatment with subcutaneous Silastic P implants (336 behavior tests). P treatment decreased sexual activity but not plasma T levels. To ascertain if P, like MPA, acts by decreasing the nuclear uptake of T by brain, four P-treated and four control males were euthanized 60 min after intravenous injection of 3 mCi of [3H]T. The nuclear uptake of unchanged [3H]T and its metabolites [3H]E(2) and [3H]DHT was measured in samples of brain, pituitary gland, genital tract, and liver. P, unlike MPA, did not affect the nuclear uptake of [3H]androgens by brain, but reduced by 80% the nuclear accumulation of [3H]E(2) in tissue samples containing preoptic area and the anterior part of the bed nucleus of stria terminalis, although not in samples from hypothalamus or amygdala.

Bilateral lesions of the central tegmental field (CTF) in male rats virtually eliminate mating behavior. This study examined if mating-induced Fos expression (a measure of neuronal activation) and androgen receptors (AR) are colocalized in brain and spinal cord neurons which project to the CTF. Animals received unilateral injections of the retrograde tracer Fluorogold (FG) in the lateral part of the CTF (CTFl), and 10 days later were killed after ejaculating with females. Brains and spinal cords were examined for FG transport, AR-immunoreactivity (AR-ir), and Fos-immunoreactivity (Fos-ir). AR-ir and Fos-ir were visualized with fluorescence microscopy using cyanine-conjugated and fluorescein-conjugated secondary antibodies. The CTFl received projections from AR-containing neurons in forebrain structures (bed nucleus of stria terminalis, medial preoptic area, lateral and ventromedial hypothalamus), in the central amygdala and various mid- and hindbrain structures (dorsolateral tegmentum, superior and inferior colliculi, pedunculopontine nucleus), and in the lumbosacral spinal cord (lamina X). Some of the AR-containing neurons in bed nucleus of stria terminalis and in the dorsal part of the medial preoptic area with projections to the CTFl were activated by mating. Most AR-containing neurons in spinal lamina X with projections to the CTFl were also activated by mating. Information from spinal cord and pontine nuclei and from outputs descending from the forebrain may be relayed in the CTFl. Thus, as part of a network of hormone-sensitive neurons linking brain and spinal cord mechanisms for mating, the CTFl could participate in the integration of visceral and somatic information relevant for sexual behavior.

Two studies were designed to document neuronal colocalization of androgen receptor immunoreactivity and mating-induced Fos immunoreactivity (AR-ir, Fos-ir) in brain of male rats and to examine the extent to which limbic and midbrain neurons that project to the preoptic area are androgen sensitive and activated by mating. Brains from male rats, killed 1 h after ejaculating with receptive females, were examined for Fos-ir and AR-ir and compared with those from control rats not given access to females. PG21 anti-AR and anti-c-fos primary antibodies were visualized by fluorescence microscopy using cyanine-conjugated and fluorescein-conjugated secondary antibodies. In mated males (Expt. 1), Fos-ir and AR-ir were colocalized in neurons of the medial preoptic nucleus (MPN), the dorsal medial amygdala (dMEA), the central tegmental field (CTF), the bed nucleus of the stria terminalis, the anterior hypothalamus, the lateral hypothalamus, and the ventral premamillary nucleus. In Expt. 2, male rats received a unilateral injection of the retrograde tracer FluoroGold (FG) in the preoptic area and four days later were killed after ejaculating with receptive females. Brains were subsequently examined for FG transport, Fos-ir and AR-ir. Fluorogold-containing neurons were present in dMEA and CTF as well as in other hypothalamic and limbic regions known to project to the MPN. In dMEA and CTF, nuclear colocalization of AR-ir and mating-induced Fos-ir was present in a proportion of FG-containing neurons. Sexually relevant information may be carried through the brain by an interconnected network of hormone-sensitive neurons.

We describe the sex differences in the development of play initiation, rough‐and‐tumble play, and mounting behavior in rhesus monkeys. There are also sex differences in the acquisition and maintenance of dominance rank under naturalistic conditions in this female‐bonded, matrilineal society. The hormonal control of adult mating behavior, as well as the behavioral patterns expressed, are quite different in males and females, but both sexes have the capacity to show bisexual patterns of behavior in special circumstances. Using high‐performance liquid chromatography and autoradiography, we found a well‐marked system of neurons that can accumulate steroids in the hypothalamus and amygdala of the fetus by 120 days of gestation. In the male fetus, plasma testosterone is high at this time, so receptors are occupied. In contrast, plasma hormones in the female remain low throughout gestation. The natural masculinization of genetic male fetuses, as well as the masculinization of females whose mothers were administe...

In male cynomolgus monkeys the synthetic progestin, medroxyprogesterone acetate (MPA), decreases testosterone (T) levels and sexual behavior, binds to progestin receptors in brain, and reduces by about 70% the uptake of [3H]androgens by both brain and genital tract tissues. To examine the behavioral effects of progesterone (P) itself, eight castrated, T-treated males were each tested twice weekly with an estrogenized female before, during, and after they were treated with two SC Silastic P implants. Data from six 4-week treatment periods were analyzed to facilitate comparisons with our previous data using MPA: i) baseline, ii) weeks 4-7 of P treatment, iii) weeks 8-11 of P treatment, iv) weeks 1-4 after P implants were removed, v) weeks 5-8 after P withdrawal, and finally vi) weeks 9-12 after P withdrawal (384 1 h behavior tests). Weekly blood samples (N = 192) were analyzed by radioimmunoassay to determine plasma levels of both T and P. P treatment, which resulted in high plasma P levels (about 44 ng/ml), produced decrements in measures of male sexual behavior and motivation that were both qualitatively and quantitatively similar to those produced by MPA treatment but, unlike MPA, P did not decrease plasma T levels or change them in any way (about 850 ng/100 ml throughout). The findings suggest that P implants may be preferable to weekly MPA injections in the treatment of male sex offenders because they require less patient compliance and may not have MPA's troubling side effects.

We previously reviewed the effects of gonadal hormones on the sexual and aggressive behavior of macaques as observed in field, outdoor colony, and laboratory studies. There were consistent similarities between findings from different observational settings, but there were also noteworthy differences which suggested the importance of social and environmental factors in modulating the effects of hormones. We now examine the role of these factors further and consider the extent to which partner preferences, familiarity between individuals, and also dominance rank can affect the behavior of male-female pairs and thereby modify the influences of hormones. The evidence suggests that all these factors are important. Hormone-dependent short-term partner preferences appear to be critical for the formation of consort bonds and to facilitate mating between unfamiliar partners. Socially based partner preferences tend to dampen hormonal influences and may lead to long-term familiarity. Long-term familiarity decreases sexual interactions and may be a proximate mechanism underlying incest avoidance and periodic male troop transfers. Both males and females exhibit mate competition under certain conditions, and their dominance rank can modify sexual and aggressive behavior by either optimizing or reducing hormone-dependent changes. These interaction effects between social and hormonal variables also have relevance for the design and interpretation of laboratory experiments. © 1996 Wiley-Liss, Inc.

Copulatory behavior was studied in five groups of sexually experienced, gonadally intact male rats in which: (i) the nonsteroidal aromatase inhibitor Fadrozole (CIBA-Geigy CGS 16949A) was delivered bilaterally (0.756 microgram in 6.0 microliters saline in 24 h to each side) into the medial preoptic area (POM) together with normal saline given s.c. via osmostic minipumps (n = 10); (ii) normal saline was delivered bilaterally into POM together with the same dose of Fadrozole s.c. (n = 9); (iii) Fadrozole was delivered bilaterally into the lateral preoptic area together with normal saline given s.c. (n = 6); (iv) Fadrozole was delivered bilaterally into the cerebral cortex together with normal saline given s.c. (n = 6), and (v) unoperated controls (n = 14). Mounting and ejaculation were significantly decreased in rats receiving Fadrozole in POM compared with the behavior of rats in the other 4 groups. Few differences occurred between rats in the latter 4 groups, all of which continued to mate. The H222 and ER-715 anti-estrogen receptor (ER) antibodies were used to examine the distribution of ER immunoreactive (ERir) neurons in hypothalamic and limbic sites in gonadectomized controls and in some of the rats in groups i, ii and v. Since labeling of ERir neurons in rat brain with the H222 anti-ER antibody is reported to be inhibited by estrogen, it was used here to identify regions (with staining) where the aromatization of testosterone (T) into estradiol (E2) had been suppressed. Intense H222 ERir nuclear neuronal labeling was confined to the POM of males receiving Fadrozole in POM, and significantly more labeled neurons were found in the POM of these rats than in the POM of rats treated with saline in POM. In contrast, the ER-715 antibody, which is reported to stain neurons independently of hormonal status, labeled neuronal nuclei in hypothalamic and limbic regions of all groups, demonstrating the presence of ER. These findings show that conversion of T into E2 in the POM of the male rat is important for male rat copulatory behavior and that H222 ERir nuclear neuronal labeling can be used to identify the neurons in POM that were affected by Fadrozole.

In many vertebrates, castration and hormone replacement and, more recently, the use of aromatase inhibitors, have shown that male sexual activity is mediated by the aromatization of testosterone (T) to estradiol (E2). In macaques, however, the systemic administration of E2, either alone or in combination with androgen, failed either to maintain or to restore the sexual activity of castrated males. The present study examines the effects of administering the nonsteroidal aromatase inhibitor, Fadrozole, either alone or combined with E2, to castrated, T-treated male cynomolgus monkeys at a dose of 0.25 mg/kg/day. This dose inhibited by over 98% the conversion of T to E2 and the subsequent accumulation of the latter in hypothalamic cell nuclei. Castrated males bearing sc Silastic impants of T were each tested with an ovariectomized, E2-treated female partner before, during, and after being given minipumps delivering either Fadrozole or water (240 1-hr tests). Within 2 weeks, Fadrozole significantly reduced ejaculatory activity and male sexual motivation in the absence of changes in plasma T levels, which remained in the upper range for intact males. Additional estradiol treatment produced small but significant increases in ejaculations by three of the six males only, and measures of male sexual motivation remained unchanged (120 tests). The present results, which stand in contrast to our previous findings in macaques, support the view that aromatization of T is important for ejaculatory activity and sexual motivation in a male primate. They also suggest that exogenous E2, which reaches the brain from the systemic circulation, does not fully duplicate the behavioral effects of E2 produced locally in the brain by the aromatization of T.

In nonhuman primates, surgical castration reduces plasma testosterone levels and male sexual behavior, and testosterone replacement restores them. Chemical castration with compounds that lower plasma testosterone levels is used clinically in the treatment of certain forms of cancer and to reduce aberrant sexual behavior in male sex offenders. In the United States, medroxyprogesterone acetate (MPA) is the drug most used to help reduce serious sexual behavioral problems in men. We were therefore interested in comparing the behavioral effects of MPA treatment (40 mg once a week) in 4 intact male cynomolgus monkeys (4 pairs, 120 tests) with data from an earlier study in our laboratory on 4 males observed before and after surgical castration (16 pairs, 192 tests). Both MPA treatment and surgical castration reduced plasma testosterone to very low levels and decreased ejaculatory activity, but MPA treatment additionally affected measures of male sexual motivation (decreased numbers of male mounting attempts and increased mounting attempt latencies) which were not primarily affected by surgical astration. However, surgical castration decreased intromission ability (percentage of intromitted thrusts per test) and male yawning behavior more rapidly than did MPA treatment. This suggested a hypothesis that different mechanisms could be involved in the behavioral effects-namely, that surgical castration may act primarily via testosterone-dependent peripheral mechanisms, while chemical castration with MPA does so primarily via central mechanisms regulating sexual motivation.

The synthetic progestin, medroxyprogesterone acetate (MPA), is used to treat male sex offenders, and it is also suppresses sexual activity in male monkeys. To examine the possibility that MPA may act as an anti-androgen in the primate brain, 4 intact male cynomolgus monkeys were given MPA (40 mg i.m.) once a week for 16 weeks, while 4 control males received i.m. injections of vehicle. All males were then castrated and 3 days later were given 3 mCi [3H]testosterone ([3H]T) i.v.; 1 h after injection males were killed, and radioactivity in nuclear pellets obtained from the hypothalamus (HYP), preoptic area (POA), amygdala (AMG), septum, pituitary gland and genital tract was analyzed by HPLC. Concentrations of [3H]T and [3H]dihydrotestosterone in nuclear pellets were 65-96% lower in MPA-treated males than in controls (P less than 0.001), but the aromatized metabolite, [3H]estradiol, which was the major form of radioactivity present in nuclear pellets from HYP, POA and AMG, was unchanged. There were no differences in concentrations of [3H]T in supernatants from the tissues of MPA-treated and control males. Because the reduced nuclear uptake of androgen in brain occurred in males whose androgen-dependent behavior had been suppressed by MPA treatments, it is proposed that MPA may have anti-androgenic effects at the level of the cell nucleus in brain regions that control behavior.

Eight groups of rhesus monkeys each consisting of one male and four ovariectomized females were observed while two of the females were treated with hormones to produce artificial menstrual cycles. These were either synchronized or offset by 7-day increments. Sexually preferred females, defined by the numbers of ejaculations per test, received almost twice as many ejaculations as did non-preferred females during all synchronized and offset cycles and during all cycle phases. However, short-term changes in partner preference occurred when the midcycle phase of non-preferred females coincided with the middle or late progesterone phase of preferred females, suggesting a negative effect of progesterone on behavior during the menstrual cycle. There were highly significant differences between preferred and non-preferred partners for almost all of their sexual and social interactions, and preferred partners showed longer proximity and grooming times as well as higher levels of sexual activity. Partner preferences accounted for more of the behavioral variance between pairs than did female dominance, although males sought the proximity of dominant females independently of their partner preferences. Thus, in a setting uncomplicated by male mate competition, sexual preference by male rhesus monkeys is a robust phenomenon depending on complex interactions between dominance, hormonal status, and the individual behavior of female partners.

To examine whether estradiol might be effective in maintaining sexual behavior after castration or after testosterone withdrawal, we have observed male rhesus monkeys during daily 1-hr tests alternately with each of two ovariectomized, estradiol-treated females (four males, four females, eight male-female pairs, 798 tests). Estradiol (2-5 micrograms/kg sc/day) or vehicle was administered in counterbalanced order immediately after castration and again immediately after withdrawal of testosterone propionate treatments (800 micrograms and 1.6 mg sc/day). There were no significant differences in behavior during vehicle and estradiol treatments to indicate that estradiol helped to maintain male sexual activity. Instead, estradiol treatment tended to interfere with the capacity to intromit. This supported the results of other studies, namely, that the systemic administration of estradiol does not enhance the sexual behavior of castrated male macaques, and raises questions about the role of both aromatization and estrogen receptors in the male primate brain.

Testosterone secreted by the testis of the macaque fetus is thought to influence certain aspects of the brain’s subsequent development which may be responsible for the ontogeny of sexually dimorphic p

In contrast to some other species, the numbers of activated neurons in the brains of male and female macaques are high in both mated and unmated animals. Dual labeling with the 1D5 anti-estrogen receptor antibody and the c- fos polyclonal anti-c- fos antibody was used in 19 female cynomolgus monkeys to examine whether mating selectively increases the activation of neurons containing estrogen receptors (ER). Mated females, and social controls exposed to males without mating, were euthanized about 75 min after the start of the test, exactly 60 min after the first ejaculation (mated females, N = 7) and 75 min after the start of exposure to a male (social controls, N = 4). A second control group of unmated females ( N = 8) remained in their individual cages until euthanasia. Neuronal nuclei containing Fos immunoreactivity (Fos-ir) alone, ER-immunoreactivity (ER-ir) alone, or both Fos-ir and ER-ir, were counted in 8 brain regions, but 2 of these regions contained too few ER-ir neurons to permit analysis. The proportion of ER-ir neurons colocalizing Fos-ir was significantly higher in the preoptic area ( P = 0.027) and ventromedial hypothalamus ( P = 0.04) of mated than of control females, suggesting the selective activation of ER-containing neurons by mating in these two brain regions known to be important in the control of female mating. The proportion of Fos-ir neurons not containing ER-ir was significantly lower in the cortical amygdala ( P = 0.045) of mated than in control females, suggesting a selective deactivation of neurons not containing ER-ir.

Mating activates estrogen sensitive neurons in several regions of male rat brain, including the medial amygdala (MEA). Infusion of the aromatase inhibitor, Fadrozole, into the MEA reduced mating, presumably by inhibiting conversion of testosterone (T) to estradiol (E(2)). We investigated whether administering E(2) locally into the amygdala (AMG) would maintain sexual behavior in male rats given systemic Fadrozole to eliminate E(2) elsewhere in the brain. Gonadally intact male rats were divided into two matched groups, based on ejaculatory performance in weekly tests with receptive females. All males received 0.29 mg/kg/day sc Fadrozole and bilateral implants to AMG. E(2)-in-AMG males (N=6 experimentals) received implants tipped with a cured mixture of E(2) in Silastic Medical Adhesive, whereas Vehicle-in-AMG males (N=6 controls) received implants tipped with cured adhesive alone (without E(2)). In E(2)-in-AMG males, postoperative mount and intromission frequency did not differ significantly from pretreatment baseline levels, but ejaculation frequency declined significantly (P.01). Conversely, in Vehicle-in-AMG males, postoperative mounts and intromissions (P.01) and ejaculations (P.01) declined significantly. Postoperative mount and intromission frequency of Vehicle-in-AMG males was significantly lower than that of E(2)-in-AMG males (P.01), but ejaculation frequency did not differ significantly between groups. This suggests that E(2)-sensitive AMG neurons are important for sexual arousal but not ejaculatory performance.

The theoretical foundation of ethology is that behavior, like morphology, is adaptive and subject to selection pressures, and that it may have a genetic basis and phylogenetic history. As with morphological and anatomical features, a behavioral trait can best be understood by determining (1) the physiological and environmental factors regulating it (its immediate or proximate mechanisms), (2) its development in the individual (ontogeny), (3) its function in terms of the advantages it confers on the animal, and (4) its evolutionary development (phylogeny).

A critical task for all living organisms is to obtain from their environment the nutrients required for energy expenditures, growth, and reproduction, and, in the short term, to maintain by homeostatic processes the constancy of the internal milieu. These various needs are mediated by behavioral mechanisms such as appetite and hunger, which lead to food-seeking behavior. Particularly in the human, these mechanisms can go awry and this results in disturbances in the control of body weight, leading to obesity or starvation.

Reproduction encompasses behaviors that range from the identification and courtship of a suitable mate to the successful rearing of offspring. Behavioral mechanisms determine the social, mating, and parental care systems of a particular species, and depend on complex interactions between anatomy and physiology on the one hand, and environmental factors, notably, habitat and predation, on the other. For example, high predator pressure may promote greater defense of young and, in turn, the extent to which the male can effectively contribute to this defense helps to determine the mating system (Chapter 15).

Chapter 2 dealt with specializations in the sender of signals, but there are also genetically programmed specializations in the receiver of signals coming from the environment or from social companions. So there can be a genetic basis for receiving as well as sending signals with adaptive significance. This is important because of the many hundreds of bits of sensory information with which animals are bombarded every moment of the day and night. Specialization in the receiver requires information reduction brought about by selective filtering, which helps to separate relevant from irrelevant information. This filtering can be considered on two separate levels: perception and attention.

Animals need to orient themselves to various environmental stimuli to find shelter (nests, lairs, burrows), food, and mates, to nurture their young, to escape predators, and, the primary topic of this chapter, to stay within or return to favorable environments. Orientation as used here comprises turning the body in a particular direction, together with movement over short distances, while navigation is the term reserved for long-distance travel, including migration. Orienting stimuli can involve several different sensory modalities. Visual stimuli include the sight of mates, predators, or prey in many birds. Acoustic stimuli are used in echolocation by bats and porpoises to avoid obstacles and find prey. Chemical stimuli include insect and mammalian pheromones that are used to locate mates. Tactile signals enable male clawed frogs to detect an appropriate mate. Sharks use electrical fields to detect prey buried in sand, while certain snakes use thermal cues to detect warm-blooded prey. In addition to signals produced by animals, a variety of other exteroceptive cues, such as gravity, light, temperature, barometric pressure, humidity, magnetic fields, and air and water currents, can serve as orienting stimuli within an animal’s immediate environment.

The attempt to understand and classify the behavior of animals, and in particular that of humans, has engaged scholars for many centuries, at least since the time of the Greek philosophers Aristotle and Plato. Ethology developed from zoology, that is, from the study by naturalists of animals in their natural habitat, whereas psychology developed from philosophy. Much of the difference between the theoretical and methodological approaches taken by ethologists and psychologists can be traced to their different origins. The following sections briefly summarize the principal branches of the behavioral sciences, ethology, and comparative psychology, the controversies between them during the 1950s and 1960s, and the subsequent synthesis that has developed into the modern study of animal behavior. This may be the most difficult chapter in the book to master.

Trivers (1972) defined parental investment as “any investment by the parent in an individual offspring that increases that offspring’s chances of surviving (and hence reproductive success) at the cost of the parent’s ability to invest in other offspring.” This includes investment in the survival of gametes and embryos as well as in the parental care of offspring after hatching or birth, until they become independent. In many species, parental care is virtually absent: In some fish, huge numbers of eggs and sperm are released into the water during spawning; fertilization and the survival of eggs and hatchlings are left to chance. In other species, the female, the male, or both provide parental care by (1) ensuring a food supply; (2) regulating the immediate environment, for example, fish fanning eggs to provide oxygenated water and birds incubating eggs; and (3) protecting the offspring from predators; and, in animals with complex brains, by (4) serving as models for acquiring social and hunting skills. Provision of food can involve quite bizarre mechanisms, including the cannibalization of eggs and younger embryos within the mother’s oviduct by other sand shark embryos, so that usually only one embryo remains. Female digger wasps lay an egg into a paralyzed, but not dead, honeybee upon which the larva feeds. In an African species of social spider, the mother makes the supreme sacrifice by being totally devoured by her young. Protection from predators can also take an unusual form. In an African mouth-breeding cichlid fish, Haplochromis, the female picks up her eggs with her mouth immediately after laying them and simultaneously picks up male sperm during attempts to pick up the “dummy” eggs on the anal fin of the male. Fertilization, incubation, and hatching all occur within her mouth, to which the fry continue to return at night and when threatened.

The following discussion assumes that the reader has taken a course in introductory and Mendelian genetics and has a basic understanding of its terminology, principles, and role in evolution. Briefly, within the nucleus of every cell except the gametes, most species have pairs of homologous chromosomes, each consisting of a long strand of the molecule deoxyribonucleic acid (DNA), with a centromere near one end. One chromosome of each pair is derived from the father and the other from the mother, and both contain the same gene sequence. Perhaps the most important discovery in biological science during the twentieth century, for which the 1962 Nobel Prize for Physiology or Medicine was awarded to Watson, Crick, and Wilkins, was the structure of DNA, a double helix consisting of two intertwined sugar-phosphate strands connected by a series of four bases, adenine pairing with thymine, and cytosine with guanine (Watson & Crick, 1953). This structure showed how chromosomes replicate themselves, and thereby the genetic code they contain, during cell division. Chromosomes consist of many genes, each being a section of chromosome at a specific locus that contains instructions for producing a particular protein that, together with others, helps to determine the development, structures, and physiological functions of the organism. In addition to the autosomes, there are two sex chromosomes that are heterologous in one sex, for example, XY in male mammals and WZ in female birds. Humans have 46 chromosomes, 22 pairs of homologous autosomes, together with a pair of sex chromosomes.

Mating was studied in sexually experienced, gonadally intact male rats assigned to two surgical groups matched on the basis of mean mounting frequency during behavioral screening trials conducted prior to the study. Estradiol (E 2 ) was delivered bilaterally into the medial preoptic area (MPO) of experimental males by means of hormone-coated implants, and fadrozole was given sc (0.25 mg/kg/day) via osmotic minipumps to block E 2 formation from testicular testosterone throughout the brain. Control males received blank bilateral implants in the MPO and sc fadrozole. After the completion of behavioral testing, immunocytochemical comparisons of the brains from experimental and control rats were made using the H222 antiestrogen receptor (ER) antibody, whose labeling is inhibited by the presence of E 2 . The histology demonstrated that E 2 was confined exclusively to the MPO of experimental males but was absent throughout the brains of controls. In controls, mounting decreased significantly by the 7th day after surgery compared with presurgical levels and did not recover. In contrast, on all postsurgical days, the mounting frequency of the experimental group was significantly higher than that of controls. Although experimental males also showed an initial, significant postsurgical decline in mounting frequency, it recovered completely by the 28th postoperative day. Ejaculations declined significantly after surgery in both groups but, unlike in controls whose performance remained low, ejaculations in experimental males partially recovered and were significantly higher than in controls during the postoperative period. Results showed that ER-containing neurons in the MPO influence male rat copulatory behavior.

The c-fos polyclonal anti-c-fos antibody was used to examine the effects of mating on Fos expression in brain neurons of 11 male macaques. Behavior tests were for 30 min, five males were unmated, four were mated, and two were social controls. Mated males were killed 60 min after ejaculation. Social controls were paired with females, but mating did not occur. Fos immunoreactive (Fos-ir) neuronal nuclei were counted in nine brain regions extending from the medial preoptic to the mammillary body area of all males. In contrast to previous reports on nonprimate laboratory species, overall there was as much Fos-ir in unmated as in mated males. Moreover, there was significantly less Fos expression in four brain regions (known to contain steroid receptors), namely, ventromedial hypothalamus, arcuate nucleus, lateral mammillary area, and bed nucleus of stria terminalis, of mated than of unmated males. There were no significant differences between mated and unmated males in the 5 other brain regions studied. These findings may reflect taxonomic differences between primates and nonprimates, or result from greater neural activation in feral animals maintained in a laboratory than in domesticated, inbred laboratory species. The simplest interpretation would be that neural activity in the male primate is turned off by mating in some brain sites but not in others.

This study was designed to determine the extent to which Fos immunoreactivity (induced either by mating or noncontact sociosexual interaction) and androgen receptor (AR) immunoreactivity are colocalized in brain and spinal cord of male rats. Some males (Mated) were allowed to mate to ejaculation; others (Social Controls) were placed with females but physical contact was prevented by a wire mesh screen; remaining males (Isolated) were placed alone in the test jar for the duration of the test period. After testing, brains and spinal cords were examined for AR and Fos immunoreactivity (ir). PG21 anti-AR and anti-c-fos primary antibodies were visualized by fluorescence microscopy using cyanine-conjugated and fluorescein-conjugated secondary antibodies. In both brain and spinal cord, the number of Fos-ir neurons varied according to group: Mated males > Social Controls > Isolated males. Fos was highly localized in subsets of AR-ir neurons within the medial preoptic nucleus, bed nucleus of the stria terminalis, dorsomedial nucleus of the amygdala, and central tegmental field. Fos was also localized in subsets of AR-ir neurons within the L5, L6, and S1 segments of the spinal cord. Spinal cord concentrations of AR-ir and Fos-ir neurons were greatest in Lamina X, and the vast majority of Fos-ir neurons in the dorsal part of Lamina X were also AR-ir. Thus, in both brain and spinal cord, androgen-sensitive neurons are active during mating, and transmission of sexually relevant information from cord to brain is probably accomplished via hormone-sensitive spinal neurons.

Sexual motivation and behavior decreased in male cynomolgus monkeys given either Depo-Provera (medroxyprogesterone acetate, MPA), which reduces androgen uptake by brain, or the nonsteroidal aromatase inhibitor, Fadrozole, which virtually eliminates the conversion of testosterone (T) to estradiol (E2) in brain. This suggested that both unchanged T and E2 are important for the control of male primate sexual behavior, but combined treatment with MPA and Fadrozole did not have the anticipated summatory effects in intact males: the behavioral decrements when MPA-treated males were given Fadrozole were about half those observed when Fadrozole was given alone. The present study tested the hypothesis that Fadrozole suppressed the behavioral effects of MPA by preventing the induction by E2 of progestin receptors in the brain to which MPA binds. Eight castrated, T-treated males were each tested with an estrogenized female i) during baseline, ii) during MPA treatment, iii) during treatment with MPA and Fadrozole together, and iv) with E2 treatment added to condition (iii) (256 1-h behavior tests). All dosages were those used in previous studies. Sexual motivation, as reflected in mounting attempts and mounting attempt latencies, was further diminished by E2 treatment in males receiving both MPA and Fadrozole, but ejaculatory activity was not changed. Immunocytochemistry demonstrated that the distributions of progestin and androgen receptors were little affected by MPA treatment, and that progestin receptor immunoreactivity was almost completely abolished in the brains of males receiving both MPA and Fadrozole but present in those receiving additional E2 treatment, findings that supported the hypothesis.

A polyclonal antibody, PA1, raised in a rabbit against fusion proteins containing fragments of the human prostatic androgen receptor (AR) was used to map the distribution of AR-like immunoreactivity in the brains of adult male and female cynomolgus monkeys. PA1 AR-immunoreactive (ARir) labeling occurred in the cell nuclei and, more weakly, in the cytoplasm of brain cells. The PA1 ARir labeling occurred primarily in brain regions previously shown on the basis of gonadal steroid autoradiography to contain androgen receptors. However, the distribution of PA1 ARir staining was substantially more restricted than that of autoradiographic labeling using 3H-androgens. The pattern of PA1 ARir labeling was closely similar between animals and occurred in the lateral septum, medial preoptic area, bed nucleus of stria terminalis, anterior, cortical, accessory basal and medial amygdala, several hypothalamic nuclei including the supraoptic, anterior, paraventricular, ventromedial and arcuate nuclei, and the premammillary nucleus. No significant sex differences were observed. With the exception of the supraoptic nucleus, reported not to be labeled by autoradiography, earlier autoradiographic findings and the current immunocytochemical results, although not congruent, have noteworthy similarities.

We previously reviewed the effects of gonadal hormones on the sexual and aggressive behavior of macaques as observed in field, outdoor colony, and laboratory studies. There were consistent similarities between findings from different observational settings, but there were also noteworthy differences which suggested the importance of social and environmental factors in modulating the effects of hormones. We now examine the role of these factors further and consider the extent to which partner preferences, familiarity between individuals, and also dominance rank can affect the behavior of male-female pairs and thereby modify the influences of hormones. The evidence suggests that all these factors are important. Hormone-dependent short-term partner preferences appear to be critical for the formation of consort bonds and to facilitate mating between unfamiliar partners. Socially based partner preferences tend to dampen hormonal influences and may lead to long-term familiarity. Long-term familiarity decreases sexual interactions and may be a proximate mechanism underlying incest avoidance and periodic male troop transfers. Both males and females exhibit mate competition under certain conditions, and their dominance rank can modify sexual and aggressive behavior by either optimizing or reducing hormone-dependent changes. These interaction effects between social and hormonal variables also have relevance for the design and interpretation of laboratory experiments. © 1996 Wiley-Liss, Inc.

Our previous studies showed that treating castrated, testosterone-treated male cynomolgus monkeys with Depo-Provera (medroxyprogesterone acetate, MPA) decreased ejaculatory performance and also measures of male sexual motivation by about 40%. Similarly, treating castrated, testosterone-treated males with the nonsteroidal aromatase inhibitor, Fadrozole, decreased ejaculatory performance and male sexual motivation again by about 40%. These behavioral decrements are, of course, mediated by totally different mechanisms. We have therefore hypothesized that both unchanged T and E2 might be important for the control of sexual behavior in this male primate, and the present study examined the consequences of administering Fadrozole at a dose of 0.25 mg/kg/day to intact male cynomolgus monkeys being treated with 40 mg/week MPA. Intact males were each tested with an ovariectomized, E2-treated female partner (i) before treatment, (ii) during treatment with MPA alone, and (iii) during treatment with MPA and either Fadrozole or water administered SC by osmotic minipumps. As in previous studies, MPA significantly decreased plasma T levels and sexual behavior. But additional treatment with Fadrozole resulted in a rapid increase in plasma T levels although causing a further decline in sexual behavior. Results supported the view that both unchanged T and its aromatized product are important for ejaculatory activity and sexual motivation in the primate. Fadrozole's effect on plasma T may have been due to the elimination of the negative feedback of E2 on the hypothalamic-pituitary-gonadal axis.

Medroxyprogesterone acetate (MPA), a synthetic progestin with androgen-depleting activity, is used to treat the deviant behavior of male sex offenders. In male cynomolgus monkeys, MPA reduces plasma testosterone (T) levels and sexual behavior, but the behavioral effects are clearly different from those of surgical castration. Because MPA is selectively taken up in unchanged form by the nuclei of neurons in the hypothalamus and preoptic area of male cynomolgus monkeys, and because it interferes with the uptake of T throughout the brain and pituitary gland, we have proposed that the behavioral effects of MPA may be mediated by brain mechanisms regulating sexual motivation that are relatively independent of circulating T levels. To test this hypothesis, eight castrated male cynomolgus monkeys bearing Silastic T implants SC were each observed during 60 min behavior tests with an ovariectomized, estrogen-treated female throughout three 4-week periods separated by 4-week periods without testing. After the first 4 weeks of testing, males received weekly IM injections of 40 mg MPA (six males) or vehicle (two males); the dose of MPA being equivalent on a body weight basis to those used clinically. Although plasma T was maintained in the upper range for intact males throughout the study, MPA treatment resulted in significantly decreased ejaculations and mounting attempts by weeks 5-6. These results demonstrated that the inhibitory effects of MPA on male behavior were independent of the reduction of plasma T levels, which points to a direct action on brain mechanisms controlling male sexual behavior.

At certain times during gestation, the testes of the fetal macaque produce plasma levels of testosterone (T) that are similar to those of adults. It is thought that testosterone acts on the brain via estrogen and androgen receptors to organize the development of sexually dimorphic neural structures that underlie sex differences in behavior. To test the proposition that there are male-female differences in the occupation of steroid receptor binding sites during fetal development in the cynomolgus macaque, we have compared the uptake of [3H]T and its metabolites in: (1) 5 intact males (plasma T 571.2 +/- 215.5 ng/100 ml); (2) 5 intact females (33.8 +/- 25.2 ng/100 ml); (3) in 5 males orchidectomized in utero (14.6 +/- 5.7 ng/100 ml). About 1 week after fetal gonadectomy or sham-operation, all fetuses were given 500 microCi [3H]T s.c. and were then delivered 60 min later by Cesarean section. Brains were removed and dissected into blocks containing the hypothalamus and preoptic area, amygdala, hippocampus, and midbrain. Samples of cerebral and cerebellar cortex were also obtained. Purified nuclear pellets were prepared by centrifugation through 2 M sucrose and were extracted into ether and analyzed by high performance liquid chromatography. Hypothalamic nuclear concentrations of [3H]E2 in intact males (847 +/- 195 dpm per mg DNA) were significantly lower than those in sham-operated females (2147 +/- 542 dpm per mg DNA) (P less than 0.05), but those in orchidectomized males (2233 +/- 345 dpm per mg DNA) were similar to concentrations in females.(ABSTRACT TRUNCATED AT 250 WORDS)

Medroxyprogesterone acetate (MPA) is used clinically to treat male sex offenders, but there are conflicting reports about its effects on aggression. To investigate these matters in a nonhuman primate, four intact male cynomolgus monkeys were studied in a testing paradigm that involved the presence of a caged, aggression-arousing stimulus male either immediately before or during a pair-test with an ovariectomized, untreated female partner. After two 4-week periods of pretreatment baseline, males received weekly injections of 40 mg MPA either alone (two 4-week treatment periods) or in combination with testosterone replacement with sc implants (one period) and additional daily injections of 2 mg testosterone propionate (two periods). MPA was then withdrawn while testosterone replacement continued (three periods). The testing paradigm was effective in maintaining aggression, especially male-male aggression, for many months. Male-male aggression increased with MPA treatment, and increased further with testosterone replacement, whereas male-female aggression tended to change in the opposite direction. As in earlier studies, MPA decreased both plasma testosterone and male sexual activity, but restoring plasma testosterone levels in treated males failed to restore their sexual activity. MPA therefore has behavioral effects that are not mediated primarily by its suppression of circulating androgens.

In social macaques, sexual, aggressive and social interactions between a male and female occur in a complex setting in which the presence of other members of the group may exert powerful, long-lasting effects. We have studied the effects of the presence of a second male, either immediately before or during pair tests, on the behavioral interactions of male cynomolgus monkeys with their female partners. Twenty-minute tests were conducted in a large room containing a small compartment that confined a second male. Each of 8 males served in turn both as a test male and as a second male (stimulus male)(4 females, 8 male-female pairs, 480 pair-tests). After 5 weeks of pair-testing with a stimulus male absent to establish behavioral baselines, the test conditions were changed daily during the next 5-week period in the following way: (1) pair-test immediately after the test male was observed with the stimulus male (Mondays), (2) control pair-test (Tuesdays), (3) pair-test in the presence of the stimulus male (Wednesdays), and (4) control pair-test (Thursdays). A final 5-week control period of pair-testing followed with the stimulus male absent. Stimulation of a test male by a second male either immediately before or during the pair-test had highly significant but different effects. Ejaculatory activity increased in tests that followed stimulation, mainly in males dominant to the stimulus male, while sexual and social activity decreased in tests during stimulation, but mainly in males subordinate to the stimulus male. The findings suggested that dominance confers a mating advantage on males even when there is no opportunity for mating interference or active mate competition.

The Publisher regrets that this article was published containing an error. Fc-fos_ should appear as Fc-fos [4]_ in the second line of the abstract. Please see the complete corrected abstract as it should appear below. In contrast to some other species, the numbers of activated neurons in the brains of male and female macaques are high in both mated and unmated animals. Dual labeling with the 1D5 anti-estrogen receptor antibody and the Fc-fos [4]_ polyclonal anti-c-fos antibody was used in 19 female cynomolgus monkeys to examine whether mating selectively increases the activation of neurons containing estrogen receptors (ER). Mated females, and social controls exposed to males without mating, were euthanized about 75 min after the start of the test, exactly 60 min after the first ejaculation (mated females, N =7) and 75 min after the start of exposure to a male (social controls

Reproductive success in many mammals depends on synchrony between copulation and ovulation, which is insured by the phenomenon of heat in the female. Certain anthropoid primates including rhesus monkeys do not show heat but may copulate throughout the menstrual cycle, especially when pairs are isolated from conspecifics. In social groups, however, mating mostly occurs around midcycle. We wished to test the hypothesis that copulations are more closely linked to ovulation when males have simultaneous access to several females in different cycle phases. Artificial menstrual cycles were therefore induced by giving hormones to ovariectomized female rhesus monkeys observed in small social groups that each consisted of four females and one male. The cycles of two hormone-treated femlab in each group were either made to synchronize or be offset by 7-day increments so that the estradiol peak of one female occurred 7 days before, and 7 and 14 days after, the estradiol peak of the other. Radioimmunoassay of plasma samples (N = 224) confirmed the timing of the estradiol peaks. Results from eight unique male-female groups (4 males, 8 females, 16 male-female pairs, 718 tests) fully supported the hypothesis. Compared with synchronized cycles, the amplitudes of rhythmic changes in offset cycles were reduced for ejaculations made by males but greatly enhanced for ejaculations received by females. We propose that this socio-hormonal integration of behavior in the group is highly adaptive and enhances the reproductive success of both males and females.

Observations on oppositely sexed pairs of M. fascicularis and M. mulatta revealed certain differences. M. fascicularis showed single-mount copulations, higher potency, less grooming activity, and milder but more frequent aggressive exchanges than the rhesus monkey. These differences might be due to the lower dominance gradient between the sexes and less sexual dimorphism in M. fascicularis than in M. mulatta. There were changes in the sexual, grooming, and aggressive interaction in relation to the menstrual cycle, indicating the suitability of M. fascicularis for hormone-behavior studies. Comparison of data from 30 and 60 min tests showed that important behavioral changes did not become apparent unless animals were given enough time to interact.

To determine the threshold doses of testosterone propionate (TP) that cause clear-cut behavioral changes in the sexual behavior of castrated male cynomolgus monkeys, observations were made on three males during successive 5-week treatment periods while they received daily subcutaneous doses of 100 micrograms TP increasing in octaves to 25.6 mg TP. Males were tested with each of the same two ovariectomized, estrogen-treated females (6 pairs, 330 1-hr behavior tests). To mimic the diurnal plasma testosterone rhythm, TP injections were given at 1600 hr and blood samples were obtained at 0800 hr (141 samples). Male ejaculatory activity increased at the threshold dose of 200 micrograms TP per day giving plasma testosterone levels of 830 ng/100 ml, which is in the physiological range of 600-1600 ng/100 ml for intact males. This threshold dose was eight times higher than in rhesus monkeys on a dose per kilogram body weight basis. There was a further marked increase in ejaculatory performance at higher doses (6.4 to 25.6 mg) giving supraphysiological plasma levels of 4000-9000 ng/100 ml. There were individual differences in the behavioral changes occurring with TP treatment, and the female partner modulated the effects. These findings were generally similar to those obtained with male rhesus monkeys, but certain species differences were noted.

Changes in direct and redirected aggression and in plasma testosterone levels were studied during a 39-month period in eight male rhesus monkeys maintained under laboratory conditions in a constant photoperiod. Males were tested with the same four ovariectomized, estrogen-treated females (32 pairs, 6357 one-hour tests), and plasma samples were obtained weekly at 0800 and 1600 hr and every two weeks at 2200 hr (2630 samples). Four males remained intact throughout and four males were castrated and received testosterone implants subcutaneously at the start of the second year. Annual changes in male aggression continued to occur at the expected time in the autumn in both intact and castrated males which indicated a degree of independence of the behavior from the photoperiod and from changes in plasma testosterone. There was a highly significant temporal association between 0800 hr testosterone and direct aggression occurring 3–4 weeks later during the first year, but this association was lost in subsequent years. Although the annual rhythms in plasma testosterone persisted for three years in the intact group, the maxima for the hormonal and the behavioral changes drifted apart in the constant photoperiod. The view is propounded that essentially independent long-term endocrine and behavioral rhythms are normally entrained by exteroceptive factors.

An analysis by the cosinor method of over 50,000 rapes in 16 different locations in the United States revealed statistically significant annual rhythms in 14 locations, with maxima in the summer. Changes in numbers of rapes and assaults showed similar seasonal patterns, suggesting that rape comprised a subcategory of aggressive behavior. In contrast, there was a virtual absence of seasonal changes in numbers of murders. A close relation emerged between assaults and rapes, on the one hand, and temperature, on the other, in different geographical locations. The authors hypothesize that human violence, just like aggression in nonhuman primates, is influenced by exteroceptive environmental factors.