Evidence of proceptive without receptive defeminization in male ferrets.

The latencies of 71 gonadectomized male and female ferrets to approach and interact with a sexually active stimulus male were measured after subcutaneous (sc) administration of estradiol benzoate ([EB] 0, 5, 10, or 15 μg/kg) in adulthood. Receptive responsiveness to stud males was also assessed during additional tests. Control females gonadectomized on Postnatal Day 35 displayed a dose-dependent reduction in approach latencies to the stud male that did not occur in control males castrated on Day 35. The approach latencies of males castrated on Day 20 or Day 5 were intermediate between these 2 extremes. Equivalent dose-dependent reductions in approach latencies were observed in Ss ovariectomized on Day 5 and implanted sc with silastic capsules containing either no hormone or different doses of testosterone over Days 5–20 or 20–35. Equivalent dose-dependent increments in acceptance quotients were obtained in all groups following EB treatment. Results suggest that the capacity to display the proceptive, or appetitive, components of feminine sexual behavior is normally reduced in male ferrets as a consequence of the perinatal action of testicular hormones, whereas receptive behavioral capacity is retained in males of this species. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prenatal and neonatal testosterone exposure interact to affect differentiation of sexual behavior and partner preference in female ferrets.

Implanting testosterone (T) subcutaneously over Postnatal Days 5–20 masculinized sexual behavior, reduced proceptive responsiveness, and shifted sexual preference more readily in male than in female ferrets gonadectomized on Day 5. This enhanced sensitivity of males to neonatal T was best duplicated in females exposed transplacentally to T over Embryonic Days (E) 27–39 (41-day gestation) and injected at birth with T (2.5 μg sc in oil:10% ethanol). Extended exposure of male ferrets to high levels of T, beginning shortly after the onset of testicular steroidogenesis (E25) and continuing for several hours after birth (E41) normally sensitizes their brains to the subsequent organizational effects on coital performance and sexual motivation of the relatively low levels of T that circulate in male ferrets during the first 3 postnatal weeks. (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)     

Uterine position and conditioned taste aversion.

Three experiments investigated the influence of uterine position on the performance of female offspring of female Sprague-Dawley and male Long-Evans rats in a conditioned taste aversion paradigm. 49 females that had males caudal to them in the same uterine horn (MF), 48 females with no caudal males (FF), and 24 males that had occupied a variety of different positions in the uterine horn were examined. Exps I and II confirmed a differential behavioral response by males and females during acquisition and extinction of the conditioned taste aversion. However, no differences were found between MF and FF Ss. In Exp III, in which testosterone was administered to females throughout testing, MF females showed an increased sensitivity to testosterone and a more prolonged rate of extinction than FF females. Exposure to testosterone during prenatal development heightened postnatal responsiveness to testosterone in female Ss. Results are discussed in terms of the organizational and activational effects of testosterone on behavior in a conditioned taste aversion situation. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Estradiol replacement in gonadectomized male rats alters scopolamine-induced disruptions of nonspatial learning.

Recent evidence indicates that testosterone can modulate learning in males through an interaction with the cholinergic system. However, the mechanism for this interaction between testosterone and the cholinergic system on learning remains uncharacterized and may involve several of testosterone's active metabolites. In the present study, two of the active metabolites of testosterone, 5α-dihydrotestosterone and estradiol, were administered in combination with the muscarinic receptor antagonist scopolamine (0.1-1 mg/kg, i.p.) to adult gonadectomized male rats that were trained to respond under a multiple schedule of repeated acquisition and performance of response sequences. In the acquisition component, subjects acquired a different three-response sequence each session, whereas in the performance component they responded on the same three-response sequence each session. When scopolamine was administered, it produced greater rate-decreasing and error-increasing effects in gonadally intact subjects than in gonadectomized subjects, even though gonadectomy had little or no effect on these measures under control conditions. In gonadectomized rats receiving 5α-dihydrotestosterone replacement, the disruptions produced by scopolamine were also smaller than those produced in gonadally intact subjects. In contrast, gonadectomized rats receiving estradiol replacement were as sensitive, or more sensitive, to scopolamine-induced disruptions of response rate and accuracy than those under the gonadally intact condition. These results suggest that testosterone's interactive effects with the cholinergic system on learning in gonadectomized male rats may not be mediated directly via androgen receptors, but rather by estrogen receptors following the aromatization of testosterone to estradiol. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of testosterone propionate administered perinatally on sexual behavior of female ferrets.

Conducted an experiment with 25 female and 8 male albino ferrets ( Mustela furo ). Females that received injections of testosterone propionate (TP) early in postnatal life displayed significantly more masculine behavior than did control females when gonadectomized and administered either TP or estradiol benzoate in adulthood. This increased masculine response potential was not correlated with the effects of early TP treatment on phallic development. In contrast to results obtained in most other species, perinatal administration of TP to females failed to disrupt their ability to display the behavior that is characteristic of the sexually receptive animal in estrus. When estrogenic stimulation was provided in adulthood, the receptive behavior of 3 groups of perinatally androgenized females was indistinguishable from that of both male and female controls. However, after gonadectomy and administration of TP, control males and females that had received TP prenatally plus on Day 3 were significantly more receptive than were control females. The induction of receptivity by TP was significantly inhibited by simultaneous administration of the antiestrogen MER-25. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of prior exposure on conditioned taste aversion in the rat: Androgen- and estrogen-dependent events.

Studied the effects of preexposure and gonadal hormone manipulation on the extinction of a conditioned taste aversion in 198 male Sprague-Dawley rats. In Exp I, Ss were given 1 prior exposure to sucrose at some selected time (Days 4, 2, or 1) before a 2nd exposure (Day 0) to sucrose and a LiCl injection, or they were given only a single exposure (Day 0). Under single exposure, castrated Ss extinguished the aversion faster than either testosterone-treated castrated Ss or sham-operated Ss. In Exp II, estradiol, dihydrotestosterone, and testosterone were studied by using only a Day 1 preexposure condition. The testosterone-treated group maintained the aversion for the longest period, followed by dihydrotestosterone-treated, sham, castrated, and estradiol-treated groups. In Exp III, estradiol was administered alone or in combination with 2 doses of dihydrotestosterone. Findings indicate that the outcome of behavior was dependent on the ratio of estradiol to dihydrotestosterone, with variations in this ratio resulting in fast (estrogen effect) to slow (androgen effect) rates of extinction. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Analysis of ultrasonic vocalizations emitted by residents during aggressive encounters among rats (Rattus norvegicus).

Determined the extent to which aggressive resident rats emit 40–70-kHz vocalizations and the effect of these signals on intruders. In Exp I, 16 deafened and intact intruder male Long-Evans rats were given 2 encounters with 8 resident Ss. Deafened intruders engaged in a higher duration of immobile or freezing postures than intact Ss. Exp II indicated that the augmentation of freezing found among deafened intruders was not due to an inability to detect ultrasounds made by residents since intruders encountering devocalized resident males showed no reliable differences in specific motor patterns from intruders paired with intact residents. Results demonstrate that 40–70-kHz vocalizations were produced almost entirely by intruding Ss since there were no significant changes in occurrence of these calls when resident males were devocalized. (13 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sexual dimorphism in ultrasonic vocalizations of mice (Mus musculus): Gonadal hormone regulation.

Male mice, during courtship and sexual behavior, vocalize substantially more 70-kHz ultrasounds than do females. Four experiments conducted with 109 male and female DBA/2J and ADK2F? mice demonstrated that testosterone propionate (TP) substantially increased ultrasonic emissions and mounting by ovariectomized females and that long-term gonadectomized males and females increased their amount of ultrasound production in response to TP to approximately the same levels. From these results it is suggested that the sexual dimorphism normally seen in ultrasonic vocalizations can be accounted for by the activational effects of androgen in adulthood. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Precocious mating in male rats following treatment with androgen or estrogen.

Conducted 5 experiments with 179 male Royal Victoria Hospital hooded rats. Daily subcutaneous injections of 1,000 MUg/100gm testosterone propionate of 5 MUg/100gm estradiol benzoate (EB) after postnatal Day 10 accelerated initial intromission and ejaculation in intact Ss. Precocious Ss continued to copulate after treatments were stopped. Age at the 1st display of intromission was unrelated to age at the 1st injection of EB. However, initiation of EB treatments before Day 11 was associated with rapid loss of intromission following cessation of treatment in adulthood. EB activated the 1st mating of prepuberally castrated and sham-operated Ss with nearly equal facility. Also, prepuberal castrates primed with EB subsequently intromitted after receiving fewer androgen replacement injections than control Ss. (24 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evaluation of prenatal androgen and ovarian secretions on receptivity in female and male rats.

A total of 102 male and 146 female offspring of Sprague-Dawley rats injected daily from Day 16 through Day 20 of gestation with either 2 mg of testosterone propionate (TP) in .1 ml of sesame oil or oil alone were tested for sexual receptivity following injections of 3.3 μg of estradiol benzoate (EB) and .5 mg of progesterone (P) beginning at 40, 80, or 120 days of age. At each age, neonatally gonadectomized males and females from TP-injected litters exhibited less receptivity than corresponding oil-injected controls. Prenatally androgenized females were similar to neonatally castrated oil-injected males at all ages. Ovarian implants from birth to 35 days of age significantly increased receptivity in neonatally castrated males and androgenized females. Increasing the age at which testing was initiated systematically reduced receptivity in all groups. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of paced coital stimulation on estrus duration in intact cycling rats and ovariectomized and ovariectomized-adrenalectomized hormone-primed rats.

Two experiments, with 121 female Long-Evans rats, investigated sexual behavior in intact cycling Ss and ovariectomized and ovariectomized-adrenalectomized hormone-primed Ss. A partitioned test cage was used in which the female controlled the timing of sexual contacts with males. Females received 9 or 10 intromissions in the partitioned test cage (paced) or with the partition removed (nonpaced), or they received solitary exposure to the test cage or to mounts without intromission with the use of vaginal masks. Intact cycling (Exp I) and gonadectomized hormone-primed (Exp II) Ss displayed similar patterns of contact with males. Exits from and latencies to return to the male compartment increased as the intensity of the antecedent coital stimulation increased. Cycling Ss given experience with paced or nonpaced mating on the evening of proestrus did not exhibit differences in pacing behavior on a 2nd test 17–24 days later. Those receiving paced coital stimulation showed a shorter duration of estrus than did those receiving nonpaced stimulation. Gonadectomized Ss given 3 successive doses of estradiol benzoate (20, 40, and 8 μg/kg, sc) in combination with progesterone (2 mg/kg) did not show shorter periods of estrus than nonpaced or mounts-only Ss. Results suggest that ovarian output in response to paced cervical-vaginal stimulation may contribute to the termination of estrus in the rat. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Female regulation and choice in the copulatory behavior of montane voles (Microtus montanus).

To study female choice of mating partners in montane voles, a male was tethered at each end of an elongate chamber, and an estrous female was allowed to move betweeen the 2 males and a neutral area. In Exp I, using 16 females and 32 males, females with a choice of 2 gonadally intact males copulated preferentially with 1 of them. Preferred males were more effective than nonpreferred males at gaining intromission and had more thrusts per intromission. In Exp II, with 10 females, 10 castrated males, and 10 sham-operated males, females spent more time with and mated preferentially with intact rather than castrated males. It is therefore suggested that the opportunity to copulate is reinforcing for female voles and that they display distinct preferences, correlated with copulatory stimulation, for some partners. (35 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of castration on grooming in goats

In African antelope and North American cervids, breeding males during the rut engage in less oral self-grooming, and harbor a greater density of ticks, compared with conspecific females and non-breeding males. The purpose of this study was to experimentally test the proposition that down-regulation of self grooming in some male bovids occurs via the direct or indirect action of testosterone. Domestic dairy goats (Capra hircus) were used as a model. In Experiment 1, comparative observations conducted on twelve gonadally intact male goats (bucks), nine males castrated at 3 weeks of age (wethers), and twelve intact females (does) supported the prediction that the grooming rate of intact males would be depressed relative to wethers and does. Bucks oral groomed at one-third and one-fourth the rate of wethers and does, respectively, and they scratch groomed half as much as does. There was no significant difference between wethers and does in oral or scratch grooming rates. Experiment 2 involved castration of eleven bucks from Experiment 1, followed by 2 months of observation. Similar to the pattern of other testosterone-dependent behavioral changes after castration in adult males, there was a good deal of variation in the individual grooming response of males to castration, with increases in grooming taking 2 to 8 weeks to be manifested in ten of eleven goats. Overall, castrated males oral groomed about 3 x above their intact rates, supporting the prediction that castration removes testosterone-mediated suppression of grooming. This is the first example of alteration of grooming behavior in males by gonadal androgen, and the first demonstration of enhancement of any mammalian behavior by removal of gonadal androgen.     

Experiential determinants of postpartum aggression in mice.

Explored the experiential determinants and the social controls of postpartum aggression in inbred ICR mice. In Exp I, 7 lactating females were tested repeatedly from Day 2 to Day 22 postpartum against male mice; attacks by the females continued through Day 18. Two other groups of 7 females tested only once showed diminished attacks against males by Day 14 postpartum. In Exp II, 8 females were paired with a male for 1 wk prior to parturition; they showed reliably fewer attacks on Day 2 postpartum than a group of 9 females that were isolated prior to parturition. All of these results were obtained in a standard 3-min test. A 24-hr test on Day 4 of Exp II revealed that in both groups female attacks dropped to near zero after 30 min. After female attacks declined, males initiated social behavior which occasioned vocalizations by the females. Further, males attacked in 65% of the tests and destroyed the litters of the females in 53% of the tests. The behavior of the male exerted important influences on the structure of extended female–male interactions. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of androgen on marking and aggressive behavior of neonatally and prepubertally bulbectomized and castrated male gerbils.

Exp I assessed the role of olfactory and androgenic influences on the development of scent-marking and aggressive behavior of 69 male gerbils. Ss were bilaterally bulbectomized, unilaterally bulbectomized, castrated, given a combination of bulbectomy and castration, or given a sham operation at 2 days of age. Marking and fighting were recorded prior to and after androgen treatment in adulthood. Postoperative tests revealed that neonatal olfactory bulb removal, alone or in combination with castration, virtually eliminated scent-marking and fighting. Treatment with testosterone propionate (TP) in adulthood was ineffective in facilitating marking after neonatal castration, bulbectomy, or their combination. However, Ss given TP did exhibit increased aggressiveness. The most striking increases were found in bulbectomized and bulbectomized-castrated Ss. In Exp II (117 Ss), bulbectomy, castration, or their combination at 35 days of age also reduced both marking and fighting. Androgen treatment in adulthood did, however, fully restore marking in all groups to control levels with the exception of bulbectomized-castrated Ss. Fighting was increased to extremely high levels following TP treatment in bulbectomized and bulbectomized-castrated Ss. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

DNA-protein interactions in the proximal zeta-globin promoter: identification of novel CCACCC- and CCAAT-binding proteins

The present study assessed whether prenatal androgen and estrogen exposure affected adult spatial learning and hippocampal morphology. Water maze performance, the CA1 and CA3 pyramidal cell field, and the dentate gyrus-granule cell layer (DG-GCL) morphology were assessed at adulthood (70+ days of age) in males, females, androgen-treated (testosterone propionate, TP, or dihydrotestosterone propionate, DHTP) females (2-4 mg/day), estradiol benzoate (EB)-treated females (100 microgram/day), and males treated with the antiandrogen flutamide (8 mg/day). Pregnant rats were injected daily (sc) between Embryonic Day 16 and birth; all pups were delivered by cesarean section. Flutamide-treated males were castrated upon delivery, and adult castrates were used to control for activational effects. Steroid-sensitive sex differences were observed in water maze performance in favor of males. Males had larger CA1 and CA3 pyramidal cell field volumes and soma sizes than females, which were feminized with flutamide treatment. TP and EB, but not DHTP, masculinized CA1 pyramidal cell field volume and neuronal soma size; CA3 was masculinized in both TP- and DHTP-treated females, while EB was ineffective. No effects were observed in cell density, number, or DG-GCL volume or due to adult hormone levels. Thus, prenatal androgens and estrogen influence sex differences in adult spatial navigation and exert differential effects on CA1 and CA3 pyramidal cell morphology. Hence, in addition to the previously reported postnatal component, there is also a prenatal component to the critical period in which gonadal steroids organize the neural mechanisms underlying sex differences in adult spatial ability.     

Regulation of androgen receptor mRNA expression in hamster facial motoneurons: differential effects of non-aromatizable and aromatizable androgens

We have previously shown inherent sex differences in the levels of androgen receptor mRNA (AR mRNA) in hamster facial motor neurons (FMN). FMN of intact females contained approximately 50% less AR mRNA than their male counterparts. Gonadectomy in males down-regulated AR mRNA levels in FMN by approximately 50%, whereas no effects of gonadectomy were observed in females. Sex differences in the regulation of AR mRNA levels by exogenous testosterone propionate (TP) were also observed. In those studies, AR mRNA levels were up-regulated after 1 day of treatment with exogenous TP in FMN of gonadectomized (GDX) males and after 7 days in FMN of intact females, with no effects in GDX females. Since TP is aromatizable to estrogen, and given recent findings of transient expression of estrogen receptors (ER) in rodent FMN, the effects of dihydrotestosterone (DHT), a non-aromatizable form of the steroid, on AR mRNA expression in hamster FMN were examined in the present study. If testosterone (TES) were the active hormone regulating AR mRNA levels in FMN, DHT treatment should render a similar regulatory pattern as TP, but if metabolism of TES to estradiol plays a role in AR mRNA regulation, effects of the two treatments should differ. In situ hybridization and computerized image analysis were used to quantify the regulation of AR mRNA by DHT in individual FMN of hamsters of both sexes. Exogenous DHT was administered to intact and gonadectomized (GDX) male and female hamsters by implantation of one 10-mm Silastic capsule for 1, 2 or 7 days. AR mRNA levels were significantly up-regulated in intact females at all time points of DHT exposure, with no effects in GDX groups. These results differ from previous work using TP, in which a modest up-regulation in AR mRNA levels was observed in FMN of intact females only after 7 days. As with TP, DHT exposure gradually down-regulated AR mRNA levels in FMN of intact males. Thus, DHT only regulated AR mRNA levels in intact animals, with endogenous sources of estrogen available, but not in GDX animals, with endogenous estrogens reduced by gonadectomy. Taken together, these results substantiate our previous findings of sex differences in AR mRNA levels/regulation and suggest a synergism between estrogen and androgen in the regulation of AR mRNA levels in peripheral motor neurons.     

Social play soliciting by male and female juvenile rats: Effects of neonatal androgenization and sex of cagemates.

Investigated the behavior of male and female Long-Evans hooded rats during individual exposure to nonplayful juvenile social stimuli in a novel test of play-soliciting behavior in 2 experiments examining hormonal and experiential determinants of sex differences. In Exp I, using 36 female and 18 male Ss, neonatally androgenized females engaged in play soliciting at a level equal to that of male controls and greater than that of nonandrogenized female controls. In Exp II, 52 males and 32 females were reared in unisexual and bisexual groups in order to compare long-term sex-related social experience effects on juvenile play soliciting. Males exposed only to other young males engaged in greater play soliciting than males exposed to both sexes; females, in contrast, were unaffected by sex of cagemates. Within rearing conditions, however, males engaged in greater play soliciting than females. The combined results suggest that perinatal gonadal androgen exposure effects on social play are prepotent and contribute essentially to sex differences in the initiation of social play behavior. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Testosterone potentiates scopolamine-induced disruptions of nonspatial learning in gonadectomized male rats.

Whereas research into the effects of the gonadal hormones on learning and memory has primarily focused on estrogen in females, recent evidence suggests that testosterone can also modulate learning in males through an interaction with the cholinergic system. In the present study, the interactive effects of testosterone and scopolamine (0.1- 0.32 mg/kg), a muscarinic receptor antagonist, on complex behavioral processes were investigated in male rats trained to respond under a multiple schedule of repeated acquisition and performance. In the acquisition component, subjects acquired a different 3-response sequence each session, whereas in the performance component, they responded on the same 3-response sequence each session. Although gonadectomy did not disrupt responding in either component, gonadectomized rats were less sensitive to the disruptive effects of scopolamine on both response rate and accuracy. In contrast, after receiving exogenous testosterone replacement, these gonadectomized males were more sensitive to the behavioral disruptions produced by scopolamine (i.e., the effects of scopolamine were similar to those obtained in gonadally intact males). These results suggest that testosterone replacement can enhance scopolamine-induced behavioral effects in gonadectomized male rats responding under a multiple schedule of repeated acquisition and performance, a finding that is in contrast to those previously found for certain spatial tasks. Furthermore, the present findings suggest that testosterone may decrease the activity of the cholinergic system during nonspatial tasks and thereby work in concert with the antagonism produced by scopolamine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)