The role of gonadal steroid receptor activation in the restoration of sociosexual behavior in adult male rats

This work tested the hypothesis that gonadal steroid receptor activation was necessary for the restoration of several sociosexual behaviors (such as copulatory behavior, partner preference, 50-kHz vocalizations, and scent marking) in testosterone-treated gonadectomized male rats. Gonadal steroid receptors were blocked by systemic administration of the antiandrogen hydroxyflutamide, the antiestrogen RU 58668, or both antagonists simultaneously in a restoration paradigm. Inhibiting androgen receptors with hydroxyflutamide blocked the restoration of male copulatory behavior, partner preference (time spent with a sexually receptive female over a nonreceptive female), 50-kHz ultrasonic vocalizations, and scent marking. On the other hand, we did not find that blocking estrogen receptors with RU 58668 inhibited the restoration of copulatory behavior or partner preference in testosterone-treated gonadectomized male rats, even though the level of brain nuclear estrogen receptor occupation was significantly reduced to the level found in gonadectomized males. However, the restoration of scent marking and 50-kHz vocalizations were impaired by RU 58668. Blocking both nuclear androgen and estrogen receptors with the two antagonists simultaneously did not have a greater inhibitory effect than treatment with each antagonist alone. Therefore, the activation of nuclear estrogen receptors is necessary for the restoration of some, but not all, sociosexual behaviors, which are also androgen receptor-dependent. Besides nuclear estrogen receptors, there are additional, but unknown, targets of estradiol that play a role in mediating copulatory behavior in adult male rats. Moreover, the signals from multiple gonadal steroid signaling pathways converge in the regulation of some sociosexual behaviors in adult male rats.     

Restoration of sexual behavior and dopaminergic neurotransmission by long term exogenous testosterone replacement in aged male rats

PURPOSE: We investigated the effects of long-term testosterone replacement on copulatory behavior and dopaminergic neurotransmission in the medial preoptic area of aged male rats. MATERIALS AND METHODS: The rats were divided into 3 groups depending on testosterone replacement. Those in the long-term replacement group were castrated at the age of 12 months and received testosterone replacement thereafter for 12 months. In the short-term replacement group, rats were castrated at the age of 22 months and high or low dose testosterone replacement was done for 2 months. The control group consisted of aged rats 24 months old and young rats 12 weeks old, neither of which had been castrated or received testosterone replacement. We observed sexual behavior in rats of these groups. After a behavioral test, we measured the tissue concentration of dopamine in the MPOA and the change rate of the extracellular dopamine level induced by infusion of N-methyl-D-aspartic acid (NMDA) in the MPOA and compared the long-term replacement and no-replacement groups. RESULTS: The rats in the long-term replacement group showed a mount rate at the same level as that of young rats at 6 weeks after starting replacement and it was maintained to 24 months of age. Their mount rate was significantly higher than that of the rats with the short-term replacement. A significantly higher change rate of dopamine release was recognized in the long-term group; however, no significant difference in the concentration of dopamine was recognized between aged rats with long-term replacement and those without replacement. CONCLUSIONS: Aged rats (24 months old) with long-term testosterone replacement maintained almost the same level of mount behavior as young rats (12 weeks old). The results imply that long-term testosterone replacement may favorably alter the decline in the process of sexual activity with aging. The restoration by testosterone replacement of dopaminergic activity in the MPOA may be involved in the maintenance of sexual function in aged rats.     

Studies of instrumental behavior with sexual reinforcement in male rats (Rattus norvegicus): II. Effects of preoptic area lesions, castration, and testosterone.

We studied effects of lesions to the medial preoptic area (POA), castration, and testosterone replacement on instrumental and unconditioned sexual behavior in male rats. We achieved instrumental measures of sexual motivation by training males to work for an estrous female, presented in an operant chamber under a second-order schedule of reinforcement. POA lesions abolished mounts, intromissions, and ejaculation but did not disrupt instrumental responses, investigation of the female, or abortive mounting attempts. Castration abolished attempts to copulate and also caused a marked decrease in instrumental responses. Testosterone resulted in the prompt reinstatement of instrumental responses and more gradual recovery of unconditioned sexual behavior. We discuss these results in terms of the motivational and performance effects of these neuroendocrine manipulations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neonatal testosterone propionate treatment in the female gerbil: Morphological and behavioral effects.

The present experiment examined the effects of a single neonatal injection of 1 mg or 100 μg of testosterone propionate (TP) on the sexual behavior and morphology of the female Mongolian gerbil. Four groups were created: vehicle-treated males (VM), 1-mg TP-treated females (HTP), 100-μg TP-treated females (LTP), and vehicle-treated females (VF). In adulthood, tests of sexual behavior were carried out after gonadectomy and appropriate hormone replacement therapy. Results indicated that LTP, HTP, and VM animals were significantly less receptive than VF animals. In addition, VM animals displayed significantly more male sexual activity than HTP, LTP, or VF animals. Immediately after the final test for male sexual behavior, subjects were weighed, anogenital distances recorded, and scent glands measured (length and width). Results indicated that a significant degree of morphological masculinization had occurred in HTP subjects for all measures and for LTP subjects for scent gland width and anogenital distance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Causes of scent marking in female golden hamsters (Mesocricetus auratus): Specific signals or classes of information?

Odor-elicited scent marking is common among mammals, but the proximate causes of marking are not well understood. Scent marking by female hamsters in response to 8 different male odors was investigated. Two odors (flank, mouth) increased flank marking and 2 (flank, rump) increased vaginal marking; in the latter case the effects of flank and rump odors were additive. Two odors (feces, urine) decreased flank marking but did not affect vaginal marking; other odors (foot, ear, ano-genital) had no influence on either scent-marking behavior. Results show that scent marking by females is influenced by a limited number of male odors, suggesting specific effects of particular odors. Classes of information (such as sexual identity) were not relevant causes of scent marking, as some odors containing such information were effective but others were not. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of neonatal (Day 10) olfactory bulb lesions on social behavior of female golden hamsters (Mesocricetus auratus).

Found that, after neonatal (Day 10) bilateral olfactory bulbectomy (BOB; n = 16), adult female golden hamsters' scent marking and defense behavior to males was reduced relative to sham (n = 13) or neocortically lesioned (n = 11) littermate controls. The BOB aggressive and sexual behavior appeared grossly normal-15 were successfully mated, but 5 destroyed their litters. After mating, controls became more aggressive but BOB aggression decreased and had disappeared by the 2nd wk. of pregnancy. All groups ceased scent marking after mating, but controls returned to premating levels during lactation. The BOB Ss showed no scent marking, defense, or aggression throughout lactation. Unilateral olfactory bulbectomy of 6 Ss also eliminated normal social behavior during lactation, suggesting that not all the behavioral effects of olfactory damage can be attributed to anosmia. (29 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Gonadal steroids promote glial differentiation and alter neuronal morphology in the developing hypothalamus in a regionally specific manner

One of the more striking sexual dimorphisms in the adult brain is the synaptic patterning in some hypothalamic nuclei. In the arcuate nucleus (ARC) males have twice the number of axosomatic and one-half the number of axodendritic spine synapses as females. The opposite pattern is observed in the immediately adjacent ventromedial nucleus (VMN). In both cases, early exposure to testosterone dictates adult dimorphism, but the exact timing, mechanism, and site of steroid action remain unknown. Astrocytes also exhibit sexual dimorphisms, and their role in mediating neuronal morphology is becoming increasingly evident. Using Golgi-Cox impregnation to examine neuronal morphology and glial fibrillary acidic protein immunoreactivity (GFAP-IR) to characterize astrocytic morphology, we compared structural differences in dendrites and astrocytes from the ARC and VMN in postnatal day 2 rat pups from four hormonally different groups. Consistent with previous observations, testosterone exposure induced a rapid and dramatic stellation response in ARC astrocytes. Coincident with this change in astrocytic morphology was a 37% reduction in the density of dendritic spines on ARC neurons. In contrast, astrocytes in the VMN were poorly differentiated and did not respond to testosterone exposure, nor were there any changes in neuronal dendrite spine density. However, VMN neurons exposed to testosterone had almost double the number of branches compared with that in controls. These data suggest that the degree of maturation and the differentiation of hypothalamic astrocytes in vivo are correlated with the ability of neurons to sprout branches or spines in response to steroid hormones and may underlie regionally specific differences in synaptic patterning.     

Localization of hypothalamic sites for the estrogen-priming of sexual receptivity in female hamsters.

Ovariectomized female hamsters received small unilateral implants of estradiol at a variety of anterior-posterior levels of the medial preoptic area and hypothalamus. The results of an initial experiment using 27-ga. implants showed that females with estradiol implants in the ventromedial hypothalamus (VMN) or nearby anterior hypothalamus consistently showed higher levels of sexual receptivity than did females with implants farther rostral, in the preoptic area, or farther caudal, in the posterior hypothalamus. A second experiment used smaller, 28-ga. implants to compare directly the two areas at which implants were effective in the first experiment. The results confirm the findings of other recent studies of hamsters and rats by identifying the VMN as the most effective hypothalamic site for the estrogen priming of sexual receptivity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Recovery of masculine copulatory behavior from lesions of the medial preoptic area: Effects of age versus hormonal state.

Two experiments tested the hypothesis that one consequence of the hormonal activation of the onset of copulation in male rats is a reduction in the plasticity of the medial preoptic area (MPOA) with respect to its role in copulation. In Exp I, 31 male rats received 1 mg of testosterone propionate daily from 10 to 45 days of age, and 30 Ss received oil injections. Ss in each of these groups received either bilateral MPOA lesions (MPOAX) or a sham operation as juveniles (28–31 days of age). The proportions of MPOAX Ss copulating as adults did not differ for Ss previously injected with oil or testosterone. In Exp II, 33 male rats were castrated at 15 days of age. These castrated Ss as well as 34 gonadally intact males received bilateral MPOA lesions or a sham operation in adulthood. Following testosterone replacement, MPOAX Ss displayed copulatory impairments regardless of hormonal state during development. Taken together, the results of these experiments suggest that the plasticity (with respect to copulation) of the neural system encompassing the MPOA is a function of some aspect of chronological age unrelated to the rat's developmental hormonal condition prior to the time of the lesion. (40 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of unilateral hypothalamic manipulations on the sexual behaviors of rats.

Four experiments that assessed the contributions of each side of the hypothalamus to the control of sexual behavior found the following: (1) Exposing the left, but not the right, ventromedial nucleus to estrogen neonatally defeminized sexual behavior in female rats. This asymmetry did not reverse as sexual differentiation progressed. (2) Unilateral cuts lateral to the medial preoptic area disrupted mounting in females that had mounted regularly before surgery, when given testosterone. The deficits were greater when the cuts were on the left side, but a third of the females with unilateral cuts showed severe deficits regardless of the side. (3) Comparable cuts did not impair masculine sexual behavior in gonadally intact males. In fact, left-side cuts seemed to accelerate copulation in males. (4) Unilateral lesions of the ventromedial nucleus disrupted lordosis in female rats in an essentially all-or-none fashion. This effect did not vary with side. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of the hippocampal system in social odor discrimination and scent-marking in female golden hamsters (Mesocricetus auratus).

Female golden hamsters (Mesocricetus auratus) received aspiration lesions of the parahippocampal region (PARA) or electrolytic lesions of the fimbria-fornix (FNX) and were tested for their (a) discrimination between odors of individual males in a habituation-discrimination task, (b) preference for male over female odors, and (c) scent-marking in response to conspecific odors. Both lesion groups habituated to repeated presentations of a male's odor. However, only FNX females discriminated between scents of individual males, whereas PARA females did not. Neither lesion eliminated female preferences for male odors. Females with FNX lesions showed decreased levels of scent marking, but those with PARA lesions had more subtle deficits. Thus, the PARA, but not the subcortical connections of the hippocampus, is critical for discrimination of the odors of individuals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Time course of VMN lesion effects on lordosis and ultrasound production in hamsters

Lesions of the ventromedial hypothalamus (VMN) depress lordosis but increase ultrasonic vocalization in female hamsters. These changes are consistent with the behavioral incompatibility of lordosis and ultrasound production and suggest that the VMN coordinates short-term changes in these behaviors. In keeping with past results, unilateral lesions disrupted lordosis responses to contralateral flank stimulation. The change appeared within 15 min after the lesion and was much more rapid than the corresponding effect in rats. For hamsters, these findings support other evidence suggesting VMN mediation of somatosensory, not just hormonal, influences on lordosis. In a companion study, ultrasound rates became depressed within 15 min of bilateral lesion of the VMN, suggesting a role for the VMN in the short-term control of ultrasound production. Calling at later time intervals was facilitated by the lesions. The direction and time course of the lesion effects on lordosis and ultrasound production suggest that the VMN cannot easily account for the behavioral incompatibility of these 2 responses.     

Identification of types II, IX and X collagens at the insertion site of the bovine achilles tendon

The authors provide initial documentation that juvenile rats emit short, high-frequency ultrasonic vocalizations (high USVs, approximately 55 kHz) during rough-and-tumble play. In an observational study, they further observe that these vocalizations both correlate with and predict appetitive components of the play behavioral repertoire. Additional experiments characterized eliciting conditions for high USVs. Without prior play exposure, rats separated by a screen vocalized less than playing rats, but after only 1 play session, separated rats vocalized more than playing rats. This findings suggested that high USVs were linked to a motivational state rather than specific play behaviors or general activity. Furthermore, individual rats vocalized more in a chamber associated with play than in a habituated control chamber. Finally, congruent and incongruent motivational manipulations modulated vocalization expression. Although play deprivation enhanced high USVs, an arousing but aversive stimulus (bright light) reduced them. Taken together, these findings suggest that high USVs may index an appetitive motivation to play in juvenile rats.     

Electrophysiological and ultrasonic correlates of reproductive behavior in the male rat.

Monitored the ultrasonic vocalizations of 13 male Long-Evans rats and determined the correlation of these vocalizations with electrophysiological activity measured by chronically implanted hippocampal and cortical electrodes during mating with a female rat. Hippocampal theta rhythms were significantly correlated with high activity, mounting, intromissions, and preejaculatory excitatory behavior and were also significantly associated with 50-kHz short ultrasonic vocalizations. Postmount or postintromission behaviors (grooming, exploration) were closely correlated with an absence of ultrasonic vocalizations and the onset of irregular low-amplitude hippocampal EEG recordings. Long 22-kHz vocalizations occurred during the postejaculatory refractory period. Shorter 22-kHz vocalizations occurred during mating and were associated with unsuccessful intromissions or mounting attempts. Postejaculatory long 22-kHz vocalizations were significantly associated with irregular high-amplitude hippocampal EEG tracings, while preejaculatory short 22-kHz vocalizations were also accompanied by sleeplike irregular high-amplitude hippocampal EEG tracings with cortical spindling. Findings suggest that ultrasonic vocalizations are indicators of the sexual arousal of mating rats. (14 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Responses to olfactory stimuli in spotted hyenas (Crocuta crocuts): II. Discrimination of conspecific scent.

Scent marking in spotted hyenas (Crocuta crocuta) includes the deposition of anal sac secretions, or "paste," and presumably advertises territorial ownership. To test whether captive hyenas classify and discriminate individuals using odor cues in paste, the authors conducted behavioral discrimination bioassays and recorded hyena investigation of paste extracted from various conspecific donors. In Experiment 1, subjects directed most investigative behavior toward scents from unfamiliar hyenas and members of the opposite sex. In Experiment 2, male hyenas discriminated between concurrent presentations of paste from various unfamiliar females in similar reproductive states. Thus, pasted scent marks convey information about the sex, familiarity, and even identity of conspecifics. Aside from territory maintenance, scent marking may also communicate information about individual sexual status. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

5HT1A-receptors and behaviour under chronic stress: selective counteraction by testosterone

Behaviour of chronically stressed male tree shrews is characterized by a reduction in scent marking, self-grooming and overall locomotor activity. It has been proposed that this subordination behaviour is related to the down-regulation of 5HT1A-receptors occurring in distinct brain regions of the animals. The high cortisol concentrations which accompany chronic stress are supposed to induce 5HT1A-receptor down-regulation. Because chronic stress in males also decreases androgen levels we investigated whether behaviour and 5HT1A-receptor expression could be renormalized by testosterone replacement. Male tree shrews were submitted to subordination stress for 28 days, while during the last 18 days, one group was treated with testosterone and one with vehicle. Scent marking, self-grooming, and overall locomotor activity were monitored, and cortisol levels were measured in morning urine during the whole experiment. Brain 5HT1A-receptors were quantified by in vitro receptor autoradiography. Although in subordinate animals cortisol levels remained high during the testosterone treatment, 5HT1A-receptors in the hippocampal formation and the occipital cortex were renormalized to control levels by the androgen, but 5HT1A-receptors in the ventromedial thalamic nucleus did not return to base line levels. Scent marking and self-grooming behaviour were both renormalized by testosterone, but overall locomotor activity did not return to base line levels. These data indicate that a balance between glucocorticoids and androgens is necessary to maintain 'normal' numbers of the monoamine receptors. The fact that both, 5HT1A-receptors and certain behaviours can be renormalized by the sex steroid supports the view that 5HT1A-receptor are involved in the regulation of stress behaviour. However, the fact that overall locomotor activity was not returned to baseline indicates that different types of behaviour are distinctly regulated.     

Dissociable onset of cognitive and motivational dysfunctions following neonatal lesions of the ventral hippocampus in rats.

This research examined cognitive and motivational processes at different developmental stages in rats with neonatal ventral hippocampus (VH) lesions, an approach used to model schizophrenia. In Experiment 1, performance in a T-maze alternation task was assessed on postnatal days (PNDs) 22 and 23. VH-lesioned rats displayed a severe deficit relative to controls. In Experiment 2, behaviorally naive rats were tested for spontaneous alternation at PND 29. Alternation was intact in VH-lesioned rats only when successive alternations were separated by >5 s. In Experiment 3, motivation was tested in a cost-benefit T-maze task and in a saccharine-water preference test. Between PNDs 22-37, behaviorally naive rats with neonatal VH lesions displayed weaker saccharine preference than controls, but the 2 groups did not differ on the cost-benefit task. At adulthood, between PNDs 56-72, the difference on saccharine preference persisted and an impairment on the cost-benefit task emerged. Overall, these results suggest that working memory deficits observed at the weaning stage were not secondary to spontaneous alternation or motivation dysfunctions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Regulatory mechanisms of territorial marking in the Mongolian gerbil.

Reports 9 experiments with castrated male Mongolian gerbils (Meriones unguiculatus). Findings indicate that Ss can be induced to mark objects with a midventral scent gland when testosterone propionate (TP) or crystalline testosterone is implanted into hypothalamic areas. The response to TP is most evident in the preoptic area. The central amygdaloid nucleus, caudate nucleus, hippocampus, reticular formation, and medial septal nucleus are not responsive. The response is exaggerated with larger cannulas (23-21 vs. 25-27 gauge) in the preoptic area. Small implants of actinomycin D (2-2.5 mg/ml) and puromycin (1:3 with TP weight) antagonize the hormone effect. Ribonuclease (1:1 with TP by weight) appears to have a similar effect, although it is short-lived. Dihydrotestosterone implanted into the same brain area is without effect on territorial marking, even though peripheral effects are obvious. Implants of magnesium pemoline (1:1 with TP by weight), an RNA stimulant, compete with TP for effects on marking and enhance marking somewhat. (24 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Deletions in Xq28 in two boys with myotubular myopathy and abnormal genital development define a new contiguous gene syndrome in a 430 kb region

The influence of the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) on the copulatory behavior of sexually experienced male Wistar rats was investigated. L-NAME was injected i.p. 10 min before the onset of a session using a dose of 30 mg/kg (L-NAME 30 group), or 60 mg/kg (L-NAME 60 group). The copulatory sessions were terminated after the third ejaculation in the control group or after 1500 s in the L-NAME 30 and L-NAME 60 groups. L-NAME administration reduced the number of rats that achieved ejaculation by 43% and 86% in the L-NAME 30 and 60 groups, respectively. In both experimental groups only a few intromissions and an increased number of mountings were observed. An increase in the number of ultrasonic vocalizations in the 50 kHz band, a dose-dependent effect, was observed. The level of sexual motivation evaluated by mount latency was not influenced by inhibition of NO synthesis.     

Manipulation of gonadal hormones in neonatal rats alters the morphological response of cortical neurons to brain injury in adulthood.

The authors examined the effects of sex and neonatal hormones on the response of pyramidal cells (Layer III, parietal cortex) to injury of the medial frontal cortex in the adult rat. At birth, males were gonadectomized (GDX) or sham-operated. Females were given testosterone (T) or oil injections. In adulthood, rats that had been left intact at birth were GDX, and they then received bilateral medial frontal cortex lesions or sham surgery. Rats not exposed to T at birth exhibited losses of dendritic arbor (males GDX at birth) or dendritic spine density (oil-treated females). Compensation after cortical injury is dependent on the rat's sex and history of exposure to gonadal steroids. (PsycINFO Database Record (c) 2010 APA, all rights reserved)