Crowding pregnant mice affects attack and threat behavior of male offspring

Attack and threat behavior of adult male offspring of female mice crowded during the final third of pregnancy was investigated. In 5-min test pairings with an anosmic "standard opponent" which had 50 microliter of male mouse urine applied to its fur, the prenatally stressed group of males showed significantly less attack behavior; attack latency was longer and number of attacks, bites, amount of time spent attacking, and composite aggression scores were all lower, compared with the control group. Similarly, less threat behavior was observed in offspring from crowded dams; there were lower frequencies of tail rattles, rough grooms, and upright threats. Additionally, proportionally fewer males in the prenatally stressed group attacked or displayed threats. A second experiment was designed to investigate the effects of exogenous androgen on the aggressiveness of males from crowded mice: testosterone propionate administration (500 micrograms/animal/day, for 5 days prior to testing) abolished differences both in the proportion of males from crowded mice that fought and also apparently abolished differences in intensities of attack and threat behavior between groups. However, trends toward reduced aggression in prenatally crowded males remained. More detailed analysis of these responses, based only on animals that displayed aggression, revealed significantly reduced intensity of aggression in offspring from females crowded during pregnancy, indicating that testosterone propionate therapy did not completely restore this behavior. In order to reduce postnatal effects due to possible differences in mothering, all offspring were fostered to untreated mothers at birth. The results are discussed in terms of in utero exposure of male fetuses of crowded dams to stress-liberated adrenal steroids of maternal origin, and the possible consequences for the endocrine integrity of these offspring.     

Genetic determinants of aggression and impulsivity in humans

Human aggression/impulsivity-related traits have a complex background that is greatly influenced by genetic and non-genetic factors. The relationship between aggression and anxiety is regulated by highly conserved brain regions including amygdala, which controls neural circuits triggering defensive, aggressive, or avoidant behavioral models. The dysfunction of neural circuits responsible for emotional control was shown to represent an etiological factor of violent behavior. In addition to the amygdala, these circuits also involve the anterior cingulated cortex and regions of the prefrontal cortex. Excessive reactivity in the amygdala coupled with inadequate prefrontal regulation serves to increase the likelihood of aggressive behavior. Developmental alterations in prefrontal-subcortical circuitry as well as neuromodulatory and hormonal abnormality appear to play a role. Imbalance in testosterone/serotonin and testosterone/cortisol ratios (e.g., increased testosterone levels and reduced cortisol levels) increases the propensity toward aggression because of reduced activation of the neural circuitry of impulse control and self-regulation. Serotonin facilitates prefrontal inhibition, and thus insufficient serotonergic activity can enhance aggression. Genetic predisposition to aggression appears to be deeply affected by the polymorphic genetic variants of the serotoninergic system that influences serotonin levels in the central and peripheral nervous system, biological effects of this hormone, and rate of serotonin production, synaptic release and degradation. Among these variants, functional polymorphisms in the monoamine oxidase A (MAOA) and serotonin transporter (5-HTT) may be of particular importance due to the relationship between these polymorphic variants and anatomical changes in the limbic system of aggressive people. Furthermore, functional variants of MAOA and 5-HTT are capable of mediating the influence of environmental factors on aggression-related traits. In this review, we consider genetic determinants of human aggression, with special emphasis on genes involved in serotonin and dopamine metabolism and function.     

Hormones and social behavior in the lizard, Anolis carolinensis

The purpose of this experiment was to study the effects of homologous and heterologous gonadal hormones on sexual and aggressive behavior in a reptilian species. Thirty adult male and thirty adult female lizards (Anolis carolinensis) were divided into 10 groups of six each (five groups per sex) and each group was given one of five treatments: either left intact, sham-castrated and injected with the hormone vehicle, castrated and injected with the hormone vehicle, castrated and injected with estradiol benzoate, or castrated and injected with testosterone propionate. After a week of visual isolation and daily hormone injection, animals were tested four times, twice with a stimulus animal of each sex. Females treated with estrogen were receptive, but did not court. Females treated with androgen were receptive and also courted and pursued stimulus females as frequently as males given androgen. No males in any group were receptive, and thus the female appears to be more capable of heterotypical sexual behavior than the male. Castrated males failed to court. Courtship and pursuit of stimulus females was readily stimulated in males with testosterone, and weakly stimulated by estrogen. Intact males were very aggressive, but lower levels of aggression were independent of gonadal hormones, as was subordination (head-nodding). The results for aggression and subordination are interpreted with reference to naturally-occurring Anolis behavior, and the results for sexual behavior are compared with similar experiments with mammals and birds.     

Fighting experience alters brain androgen receptor expression dependent on testosterone status

Contest decisions are influenced by the outcomes of recent fights (winner–loser effects). Steroid hormones and serotonin are closely associated with aggression and therefore probably also play important roles in mediating winner–loser effects. In mangrove rivulus fish, Kryptolebias marmoratus, individuals with higher testosterone (T), 11-ketotestosterone and cortisol levels are more capable of winning, but titres of these hormones do not directly mediate winner–loser effects. In this study, we investigated the effects of winning/losing experiences on brain expression levels of the receptor genes for androgen (AR), oestrogen α/β (ER_α/β), glucocorticoid (GR) and serotonin (5-HT_1AR). The effect of contest experience on AR gene expression depended on T levels: repeated losses decreased, whereas repeated wins increased AR gene expression in individuals with low T but not in individuals with medium or high T levels. These results lend strong support for AR being involved in mediating winner–loser effects, which, in previous studies, were more detectable in individuals with lower T. Furthermore, the expression levels of ER_α/β, 5-HT_1AR and GR genes were higher in individuals that initiated contests against larger opponents than in those that did not. Overall, contest experience, underlying endocrine state and hormone and serotonin receptor expression patterns interacted to modulate contest decisions jointly.     

The effects of castration and Silastic implants of testosterone on intermale aggression in the mouse

Castration and testosterone (T) replacement were used to study developmental changes in aggressive behavioral responsiveness to androgenic stimulation. Male mice castrated at birth were less sensitive to circulating T than were prepubertal or adult castrates, but fighting was induced in neonatal castrates with a dose of androgen that produced hypertrophy of the accessory organ system in adult castrates. Gonadectomy shortly prior to pubertal increases in serum T concentration also reduced behavioral responsiveness to androgen administration. Intermale aggression was induced in prepubertal castrates only with T treatment that maintained accessory organ growth in adult castrates. The aggressive behavior of males castrated after the pubertal surge in serum T was supported with circulating levels of androgen that failed to stimulate the accessory organ system above that of oil-treated castrates. It was concluded that T stimulation during neonatal or pubertal life is not totally crucial for organization of neural substrates that mediate the ultimate expression of intermale aggression, but exposure to androgen from birth throughout pubertal development is normally required to produce maximal aggressive behavioral responsiveness to circulating T encountered in adulthood.     

Anxiety and increased 5-HT1A receptor response in NCAM null mutant mice.

Mice deficient in the neural cell adhesion molecule (NCAM) show behavioral abnormalities as adults, including altered exploratory behavior, deficits in spatial learning, and increased intermale aggression. Here, we report increased anxiety-like behavior of homozygous (NCAM-/-) and heterozygous (NCAM/-) mutant mice in a light/dark avoidance test, independent of genetic background and gender. Anxiety-like behavior was reduced in both NCAM+/+ and NCAM-/- mice by systemic administration of the benzodiazepine agonist diazepam and the 5-HT1A receptor agonists buspirone and 8-OH-DPAT. However, NCAM-/- mice showed anxiolytic-like effects at lower doses of buspirone and 8-OH-DPAT than NCAM+/+ mice. Such increased response to 5-HT1A receptor stimulation suggests a functional change in the serotonergic system of NCAM-/- mice, likely involved in the control of anxiety and aggression. However, 5-HT1A receptor binding and tissue content of serotonin and its metabolite 5-hydroxyindolacetic acid were found unaltered in every brain area of NCAM-/- mice investigated, indicating that expression of 5-HT1A receptors as well as synthesis and release of serotonin are largely unchanged in NCAM-/- mice. We hypothesize a critical involvement of endogenous NCAM in serotonergic transmission via 5-HT1A receptors and inwardly rectifying K+ channels as the respective effector systems.     

Testosterone-induced aggression in adult female mice

Silastic implants of testosterone (T) and injections of testosterone propionate (TP) were used to study the effects of ovariectomy and androgen administration on the fighting behavior of adult female mice. A dose of T previously shown to hyperstimulate accessory organ growth in adult male castrates was sufficient to induce the complete behavioral repertoire of male-like aggression in females never before treated with exogenous androgen. As determined by radioimmunoassay, blood levels of T produced by implants containing an aggression-inducing dose of T (10-mg implant) were within the range of T concentrations observed in intact males. Following treatment with a 10-mg T implant, the aggressive behavior of ovariectomized females could be fully maintained with a dose of T (0.3-mg implant) that failed to maintain weight of the accessory organs in adult male castrates. In fact, females “androgenized” were subsequently more responsive to the aggression-activating properties of T than were males castrated after prenatal and perinatal androgen exposure.     

Territorial aggression does not feed back on testosterone in a multiple-brooded songbird species with breeding and non-breeding season territoriality,the European stonechat

Testosterone mediates reproductive behaviours in male vertebrates. For example, breeding season territoriality depends on testosterone in many species of birds and in some, territorial interactions feed back on testosterone concentrations. However, the degree to which territorial behaviour and testosterone are associated differs even between species with seemingly similar life histories, especially between species that also defend territories outside the breeding season. Here, we investigate the link between territorial behaviour and testosterone in European stonechats. Previous studies found that territorial aggression in stonechats depends on testosterone in a breeding, but not in a non-breeding context. We investigated whether stonechats show a rise in testosterone during simulated territorial intrusions (STI) during the breeding season. Post-capture testosterone concentrations of males caught after an STI were not higher than those of males caught in a control situation regardless of breeding stage. However, most of the males would have been able to mount a testosterone response because the same individuals that did not increase testosterone during the STI showed a substantial increase in testosterone after injections of gonadotropin-releasing hormone (GnRH). GnRH-induced and post-capture testosterone concentrations were positively correlated and both decreased with successive breeding stages. Further, territory owners with a short latency to attack the decoy expressed higher post-capture testosterone concentrations than males with a longer latency to attack the decoy. Thus, there is no evidence for behavioural feedback on testosterone concentrations during male-male interactions in stonechats. In combination with previous studies our data suggest that testosterone functions as an on/off switch of high intensity territorial aggression during the breeding season in stonechats. The among-species variation in the androgen control of territorial behaviour may be only partly a result of environmental differences. Instead, potential differences in how territoriality evolved in different species may have influenced whether and how a reproductive hormone such as testosterone was co-opted into the mechanistic control of territorial behaviour.     

Acute effects of aspartame on aggression and neurochemistry of rats

The inverse relationship between serotonin and aggression was investigated in rats treated with aspartame, a sweetener thought to interfere with the synthesis of this neurotransmitter. Eleven adult, male Long-Evans rats received either aspartame (200-800 mg/kg, IP) or the vehicle prior to testing in a standard resident-intruder paradigm. Contrary to our hypothesis, aspartame significantly decreased aggression as shown by increased latencies to the first attack and decreased number of bites per session. Corresponding with the effects on aggression, aspartame significantly increased striatal levels of serotonin. It was concluded that high doses of aspartame reduced aggressive attack via a serotonergic mechanism while the lower dose was without effect on either variable.     

Haploinsufficiency of cytochrome P450 17alpha-hydroxylase/17,20 lyase (CYP17) causes infertility in male mice

Cytochrome P450 17alpha-hydroxylase/17,20-lyase (CYP17) is critical in determining cortisol and sex steroid biosynthesis. To investigate how CYP17 functions in vivo, we generated mice with a targeted deletion of CYP17. Although in chimeric mice Leydig cell CYP17 mRNA and intratesticular and circulating testosterone levels were dramatically reduced (80%), the remaining testosterone was sufficient to support spermatogenesis as evidenced by the generation of phenotypical black C57BL/6 mice. However, male chimeras consistently failed to generate heterozygous CYP17 mice and after five matings chimeric mice stopped mating indicating a change in sexual behavior. These results suggested that CYP17 deletion caused a primary phenotype (infertility), probably not due to the anticipated androgen imbalance and a secondary phenotype (change in sexual behavior) due to the androgen imbalance. Surprisingly, CYP17 mRNA was found in mature sperm, and serial analysis of gene expression identified CYP17 mRNA in other testicular germ cells. CYP17 mRNA levels were directly related to percent chimerism. Moreover, more than 50% of the sperm from high-percentage chimeric mice were morphologically abnormal, and half of them failed the swim test. Furthermore, 60% of swimming abnormal sperm was devoid of CYP17. These results suggest that CYP17, in addition to its role in steroidogenesis and androgen formation, is present in germ cells where it is essential for sperm function, and deletion of one allele prevents genetic transmission of mutant and wild-type alleles causing infertility followed by change in sexual behavior due to androgen imbalance.     

Anxiety and increased 5‐HT1A receptor response in NCAM null mutant mice

Mice deficient in the neural cell adhesion molecule (NCAM) show behavioral abnormalities as adults, including altered exploratory behavior, deficits in spatial learning, and increased intermale aggression. Here, we report increased anxiety‐like behavior of homozygous (NCAM^−/−) and heterozygous (NCAM^+/−) mutant mice in a light/dark avoidance test, independent of genetic background and gender. Anxiety‐like behavior was reduced in both NCAM^+/+ and NCAM^−/− mice by systemic administration of the benzodiazepine agonist diazepam and the 5‐HT_1A receptor agonists buspirone and 8‐OH‐DPAT. However, NCAM^−/− mice showed anxiolytic‐like effects at lower doses of buspirone and 8‐OH‐DPAT than NCAM^+/+ mice. Such increased response to 5‐HT_1A receptor stimulation suggests a functional change in the serotonergic system of NCAM^−/− mice, likely involved in the control of anxiety and aggression. However, 5‐HT_1A receptor binding and tissue content of serotonin and its metabolite 5‐hydroxyindolacetic acid were found unaltered in every brain area of NCAM^−/− mice investigated, indicating that expression of 5‐HT_1A receptors as well as synthesis and release of serotonin are largely unchanged in NCAM^−/− mice. We hypothesize a critical involvement of endogenous NCAM in serotonergic transmission via 5‐HT_1A receptors and inwardly rectifying K⁺ channels as the respective effector systems. © 1999 John Wiley & Sons, Inc. J Neurobiol 40: 343–355, 1999     

Disruption of the vasopressin 1b receptor gene impairs the attack component of aggressive behavior in mice

Vasopressin affects behavior via its two brain receptors, the vasopressin 1a and vasopressin 1b receptors (Avpr1b). Recent work from our laboratory has shown that disruption of the Avpr1b gene reduces intermale aggression and reduces social motivation. Here, we further characterized the aggressive phenotype in Avpr1b -/- (knockout) mice. We tested maternal aggression and predatory behavior. We also analyzed the extent to which food deprivation and competition over food increases intermale aggression. We quantified defensive behavior in Avpr1b -/- mice and later tested offensive aggression in these same mice. Our results show that attack behavior toward a conspecific is consistently reduced in Avpr1b -/- mice. Predatory behavior is normal, suggesting that the deficit is not because of a global inability to detect and attack stimuli. Food deprivation, competition for food and previous experience increase aggression in both Avpr1b +/+ and -/- mice. However, in these circumstances, the level of aggression seen in knockout mice is still less than that observed in wild-type mice. Defensive avoidance behaviors, such as boxing and fleeing, are largely intact in knockout mice. Avpr1b -/- mice do not display as many 'retaliatory' attacks as the Avpr1b +/+ mice. Interestingly, when territorial aggression was measured following the defensive behavior testing, Avpr1b -/- mice typically show less initial aggressive behavior than wild-type mice, but do show a significant increase in aggression with repeated testing. These studies confirm that deficits in aggression in Avpr1b -/- mice are limited to aggressive behavior involving the attack of a conspecific. We hypothesize that Avpr1b plays an important role in the central processing that couples the detection and perception of social cues (which appears normal) with the appropriate behavioral response.     

Neither testosterone levels nor aggression decrease when the male Mongolian gerbil (Meriones unguiculatus) displays paternal behavior

The first studies that correlated mammalian paternal behavior and testosterone levels indicated that the concentration of this steroid hormone decreases when males exhibit paternal care. However, recent studies have also shown that testosterone levels do not decrease when males display paternal behavior. In this study, we measured testosterone levels in plasma throughout the reproductive cycle of the Mongolian gerbil. Testosterone concentrations were correlated with paternal care as well as aggression. We also examined whether there is a trade-off between paternal behavior and aggression in this mammal. Our results show that Mongolian gerbil testosterone levels do not decrease when the males give paternal care. Likewise, male Mongolian gerbils exhibit high levels of aggression while displaying paternal behavior, indicating that there is no trade-off between aggression and paternal behavior. More studies are needed to determine whether testosterone is involved in the regulation of paternal behavior in this rodent.     

Effects of melatonin on the behavioral and hormonal responses of red-sided garter snakes (Thamnophis sirtalis parietalis) to exogenous corticosterone

We investigated possible interactions between melatonin and corticosterone in modulating the reproductive behavior of male red-sided garter snakes (Thamnophis sirtalis parietalis) following spring emergence. We also examined whether melatonin's modulatory actions could be explained by its potential properties as a serotonin receptor antagonist. Exogenous corticosterone significantly reduced courtship behavior of male snakes in a dose-dependent manner. Melatonin also significantly reduced courtship behavior of male garter snakes. Pretreatment with melatonin before administering corticosterone treatments further suppressed courtship behavior of red-sided garter snakes. These results indicate additive inhibitory effects of melatonin and corticosterone in modulating reproductive behavior. Snakes receiving ketanserin, a serotonergic type 2A receptor antagonist, followed by corticosterone also showed reduced courtship behavior; this serotonin receptor antagonist followed by treatment with vehicle did not significantly influence courtship behavior of male snakes. Neither melatonin nor corticosterone treatments significantly influenced testosterone + 5-alpha-dihydrotestosterone concentrations of male garter snakes, supporting a direct effect of melatonin and corticosterone on courtship behavior that is independent of any effect on androgen concentrations. We propose that a serotonin system is involved in the modulation of male courtship behavior by melatonin and corticosterone. In addition, our data support the hypothesis that melatonin may function as a serotonin receptor antagonist. Further research is necessary to discern whether the actions of melatonin and corticosterone are converging on the same pathway or if their effects on different pathways are having additive inhibitory effects on courtship behavior.     

Social Experience During Development and Female Offspring Aggression in Peromyscus Mice

Cross‐fostering between the highly aggressive, biparental California mouse (Peromyscus californicus) and the less aggressive, less parental white‐footed mouse (P. leucopus) influences female offspring attack latency in California mice, but not in white‐footed mice. Adult female California mice raised by white‐footed mice expressed longer attack latencies in a neutral‐arena test but not in a resident‐intruder test. One social cue that may be used by offspring to develop environmentally appropriate levels of aggression is the type of parental care during development. In California mice, a composite score of maternal behavior was positively associated with neutral‐arena aggression as indicated by decreased attack latency. In both species, paternal nest‐building was positively associated with neutral‐arena aggression and higher maternal retrieval behavior predicted higher offspring resident‐intruder aggression as indicated by decreased attack latency. Together, these results indicate that parental behavior has the potential to shape the development of attack latency in female offspring.     

Raphe serotonin neuron‐specific oxytocin receptor knockout reduces aggression without affecting anxiety‐like behavior in male mice only

Serotonin and oxytocin influence aggressive and anxiety‐like behaviors, though it is unclear how the two may interact. That the oxytocin receptor is expressed in the serotonergic raphe nuclei suggests a mechanism by which the two neurotransmitters may cooperatively influence behavior. We hypothesized that oxytocin acts on raphe neurons to influence serotonergically mediated anxiety‐like, aggressive and parental care behaviors. We eliminated expression of the oxytocin receptor in raphe neurons by crossing mice expressing Cre recombinase under control of the serotonin transporter promoter (Slc6a4) with our conditional oxytocin receptor knockout line. The knockout mice generated by this cross are normal across a range of behavioral measures: there are no effects for either sex on locomotion in an open‐field, olfactory habituation/dishabituation or, surprisingly, anxiety‐like behaviors in the elevated O and plus mazes. There was a profound deficit in male aggression: only one of 11 raphe oxytocin receptor knockouts showed any aggressive behavior, compared to 8 of 11 wildtypes. In contrast, female knockouts displayed no deficits in maternal behavior or aggression. Our results show that oxytocin, via its effects on raphe neurons, is a key regulator of resident‐intruder aggression in males but not maternal aggression. Furthermore, this reduction in male aggression is quite different from the effects reported previously after forebrain or total elimination of oxytocin receptors. Finally, we conclude that when constitutively eliminated, oxytocin receptors expressed by serotonin cells do not contribute to baseline anxiety‐like behaviors or maternal care.     

Sexual differentiation of androgen-sensitive and estrogen-sensitive regulatory systems for aggressive behavior

CF-1 female mice were treated with either testosterone (T), diethylstilbestrol (DES), or methyltrienolone (R1881) on the day of birth and were subsequently tested for their responsiveness to the aggression-promoting property of androgen or estrogen during adulthood. The results showed that neonatal exposure to androgen enhanced subsequent sensitivity to androgenic stimulation but did not alter responsiveness to estrogens. Neonatal estrogen treatment established the capacity to exhibit aggression in response to estrogenic stimulation in adulthood but had little effect on responsiveness to androgens. These data indicate that the androgenic and estrogenic metabolites of T have distinct roles in masculinization of the neural substrate for aggressive behavior.     

Seasonal variation in male testosterone levels in a tropical bird with year‐round territoriality

Testosterone is important in mediating investment in competing activities such as territoriality, parental care, and maintenance behavior. Most studies of testosterone function have focused on temperate species and less is known about the role of testosterone in territoriality or variation in mating systems of tropical species. Results of studies of tropical species with year‐round territoriality indicate that territorial aggression during the non‐breeding season is maintained with low levels of testosterone, and increased levels of testosterone in males during the breeding season may increase mating opportunities or aid in competition for mates. We studied seasonal variation in testosterone levels of male Red‐throated Ant‐tanagers (Habia fuscicauda), a socially monogamous species with year‐round territoriality and with high levels of extra‐pair matings (41% of young), to determine if testosterone levels increased during the breeding season. We captured males during the non‐breeding and breeding seasons and collected blood samples for hormone analysis. We found that mean testosterone concentrations were low during the non‐breeding season (0.18 ± 0.05 [SD] ng/ml, range = 0.11–0.31 ng/ml), and significantly higher during the breeding season (2.37 ± 2.47 ng/ml, range = 0.14–6.28 ng/ml). Testosterone levels of breeding males were not related to aggression levels as measured by attack rates toward a stuffed decoy or singing rates during simulated territorial intrusions. These results suggest that the higher testosterone levels of breeding male Red‐throated Ant‐tanagers may be important in an extra‐pair mating context, possibly in display behavior or mate attraction, but additional study is needed to clarify the role of testosterone during the breeding season.     

Male and female cooperatively breeding fish provide support for the "Challenge Hypothesis"

The idea that territorial aggression is regulated by androgensand that aggression itself can modulate androgen levels is wellestablished in males. In many species, females also displayaggressive behavior, yet little work has been conducted on theeffects of female aggression on hormone levels. In this study,we compared the effects of a simulated territory intrusion (amethod for testing the Challenge Hypothesis) on males and femalesof the fish, Neolamprologus pulcher. This cichlid fish fromLake Tanganyika is a particularly useful species to examinesex differences in the behavioral mediation of hormones as breedingpairs remain in a territory year round and both sexes defendthis territory against conspecific and heterospecific intruders.In our study, both sexes indeed aggressively defended theirterritory against a simulated territory intruder. In responseto intruders, both males and females displayed elevated levelsof circulating 11-ketotestosterone, but only females exhibitedincreases in testosterone. Neither aggressing male nor femalefish showed changes in estradiol levels compared to control(nonaggressing) fish. Residents were more aggressive than theintruders and won most of the interactions. However, residents(or winners) did not show higher hormone levels than intruders(or losers). We suggest that aggression commonly modulates androgenlevels in both male and female teleost fish.     

Independent control of sexual and scent marking behaviors of male gerbils by cells in or near the medial preoptic area

This research studied the role of the medial preoptic area and adjacent cell populations in androgen control of scent marking and sexual behavior in male gerbils (Meriones unguiculatus). Experiment 1 replicated previous research showing that implants of testosterone propionate in or near the medial preoptic area reinstate marking behavior in castrates. Implant sites near the diagonal band of Broca or in the posterior part of the medial preoptic area, near the anterior hypothalamus, are more effective than other sites. Experiment 2 showed that medial preoptic area lesions permanently impair sexual behavior despite testosterone stimulation. Experiments 2–4 showed that lesions in or near the medial preoptic area can also disrupt scent marking; however, this behavior gradually recovered in many lesioned males, especially if they received testosterone. The data suggest that both scent marking and sexual behavior are controlled by androgens acting on cells in or near the medial preoptic area, but the cell populations involved in these two behaviors are probably not the same.