Reproductive experience alters corticosterone and CBG levels in the rat dam.

in Physiology & Behavior (2009), 96(1), 108-14

Reproductive experience has significant effects on the brain, behavior and hormone profiles of the mother. Recent work has demonstrated that primiparous rats exhibit decreased dendritic arborizations in ... [more ▼]

Reproductive experience has significant effects on the brain, behavior and hormone profiles of the mother. Recent work has demonstrated that primiparous rats exhibit decreased dendritic arborizations in the hippocampus, and enhanced hippocampus-dependent spatial memory performance at the time of weaning compared to nulliparous and, to a lesser degree, multiparous rats. Interestingly, enhanced spatial learning and reduced dendritic arbors are seen in nulliparous female rats exposed to chronic stress or repeated corticosterone administration. Based on these observations, we hypothesized that corticosterone may be altered in primiparous rats compared to multiparous and nulliparous rats. The present study investigated whether the levels of circulating corticosterone and its binding protein, corticosteroid binding globulin (CBG), are altered with reproductive experience and pup-exposure during late pregnancy and the postpartum. Total serum corticosterone and CBG were assayed from five groups; multiparous, primiparous, nulliparous, primip-no-pups, and sensitized rats during gestation (days 14 and 19) and the postpartum period (days 1, 5, 14, 21, and 35). Results show that primiparous rats had significantly elevated total corticosterone on postpartum day 1. In addition, primiparous and multiparous rats had significantly lower CBG throughout the postpartum period than all other groups, with primiparous rats exhibiting lower levels than multiparous rats during mid-lactation. These data suggest that free corticosterone is elevated in both primiparous and multiparous dams and is elevated to a greater degree in primiparous compared to multiparous dams during lactation. Corticosterone and CBG levels were positively correlated with specific maternal behaviors during the first week postpartum in parturient rats, but not in sensitized rats, suggesting a role for corticosterone in the modulation of maternal behavior in parturient rats alone. [less ▲]

Preoptic aromatase modulates male sexual behavior: slow and fast mechanisms of action

in Physiology & Behavior (2004), 83(2), 247-270

In many species, copulatory behavior and appetitive (anticipatory/motivational) aspects of male sexual behavior are activated by the action in the preoptic area of estrogens locally produced by ... [more ▼]

In many species, copulatory behavior and appetitive (anticipatory/motivational) aspects of male sexual behavior are activated by the action in the preoptic area of estrogens locally produced by testosterone aromatization. Estrogens bind to intracellular receptors, which then act as transcription factors to activate the behavior. Accordingly, changes in aromatase activity (AA) result from slow steroid-induced modifications of enzyme transcription. More recently, rapid nongenomic effects of estrogens have been described and evidence has accumulated indicating that AA can be modulated by rapid (minutes to hour) nongenomic mechanisms in addition to the slower transcriptional changes. Hypothalamic AA is rapidly down-regulated in conditions that enhance protein phosphorylation, in particular, increases in the intracellular calcium concentration, such as those triggered by neurotransmitter (e.g., glutamate) activity. Fast changes in brain estrogens can thus be caused by aromatase phosphorylation as a result of changes in neurotransmission. In parallel, recent studies demonstrate that the pharmacological blockade of AA by specific inhibitors rapidly (within 15-45 min) down-regulates motivational and consummatory aspects of male sexual behavior in quail while injections of estradiol can rapidly increase the expression of copulatory behavior. These data collectively support an emerging concept in neuroendocrinology, namely that estrogen, locally produced in the brain, regulates male sexual behavior via a combination of genomic and nongenomic mechanisms. Rapid and slower changes of brain AA match well with these two modes of estrogen action and provide temporal variations in the estrogen's bioavailability that can support the entire range of established effects for this steroid. (C) 2004 Elsevier Inc. All rights reserved. [less ▲]

Effect of prenatal androgen receptor antagonist or aromatase inhibitor on the differentiation of neuronal Fos responses to estrous female pheromones in the rat accessory olfactory system

in Physiology & Behavior (2002), 75

Many socially relevant odors are detected in rodent species by the vomeronasal organ and subsequently processed by the accessory olfactory system (AOS). We previously found that gonadectomized male and ... [more ▼]

Many socially relevant odors are detected in rodent species by the vomeronasal organ and subsequently processed by the accessory olfactory system (AOS). We previously found that gonadectomized male and female rats treated in adulthood with testosterone propionate (TP) showed equivalent Fos responses in the AOS to odors derived from estrous females. Likewise, in contrast with numerous other mammalian species, gonadectomized female rats show surprisingly high levels of male-typical mounting behavior in response to adult TP. We tested the hypothesis that prenatal testosterone (T) exposure, acting via androgen receptors (ARs) or via estrogen receptors, masculinizes the AOS in rats of both sexes. Pregnant dams were treated with either the AR blocker, Flutamide, the aromatase inhibitor, 1,4,6-androstatriene-3,17-dione (ATD), or nothing (control) to assess the role of prenatal androgen and estradiol receptor activation, respectively, in this masculinization. Beginning at birth, male and female offspring were injected subcutaneously (sc) every other day with either ATD (pre- and neonatal ATD group) or oil vehicle (Flutamide and control groups) until postnatal Day 12. Subjects were gonadectomized as adults, hormonally treated and tested for different behaviors before having their AOS Fos responses to estrous female odors assessed. Prenatal treatment with Flutamide (but not ATD) significantly decreased anogenital distance and severely impaired intromissive and ejaculatory behaviors in males tested after TP replacement without disrupting mounting capacity in either sex. Pre- and neonatal treatment with ATD (but not Flutamide) enhanced lordosis responsiveness in males tested after sc injections of estradiol and progesterone, whereas these perinatal treatments had no effect on any aspect of masculine coital performance in either sex. After TP treatment, male and female control subjects preferred to approach a tethered stimulus female as opposed to a male, and prenatal Flutamide or perinatal ATD treatments did not modify this pattern of partner preference. Neuronal Fos responses to estrous odors were (as in previous studies) identical in the AOS of gonadectomized TP-treated control males and females. Prenatal Flutamide or perinatal ATD treatments failed to disrupt consistently this profile of Fos responses to estrous odors in the AOS of rats of either sex. These behavioral and neuroanatomical findings raise the possibility that the similar level of male-typical responsiveness to social odors that occurs in male and female rats after adult TP treatment results from nonsteroid-hormone-dependent, species-specific factors that act perinatally in the brains of rats of both sexes. [less ▲]

Sexual differentiation of odor and partner preference in the rat.

in Physiology & Behavior (1996), 60(2), 489-94

Previous studies have shown that adult male rats, in which brain estrogen formation was inhibited neonatally by SC administration of the aromatase inhibitor 1,4, 6-androstatriene-3,17-dione (ATD), show an ... [more ▼]

Previous studies have shown that adult male rats, in which brain estrogen formation was inhibited neonatally by SC administration of the aromatase inhibitor 1,4, 6-androstatriene-3,17-dione (ATD), show an altered sexual partner preference. When tested in a three-compartment box, such gonadally intact ATD males approach and mate both with the estrous female and the sexually active male, whereas normal males prefer to approach and mate with the estrous female, avoiding the stimulus male. After castration in adulthood and estradiol treatment, ATD males prefer sexually active males. Similarly treated normal males prefer estrous females, and estrous females prefer to mate with males. In the present study, we asked what stimulus characteristics of active males vs. estrous females determined the different sexual preferences of males, ATD males, and of females. Were they chemosensory cues or more distal cues such as actually seeing and hearing the stimulus animals or the reward of sexual activity with the stimulus animals? Sex differences in preference were evident when animals were given a choice between soiled bedding from estrous females and from sexually active males. ATD and control males spent significantly more time on soiled bedding from estrous females than on soiled bedding from sexually active males. Control females spent significantly more time on soiled bedding from sexually active males than on soiled bedding from estrous females. More distal cues, such as seeing and hearing the stimulus animals, revealed differences in preference between control males and females, but not between ATD and control males. Physical interaction with the stimulus animals was a prerequisite for revealing differences in preference between ATD and control males. Then, the behavior of ATD males was clearly intermediate between that of normal male and female rats. In conclusion, neonatal estradiol is important for the psychosexual development of the male rat. However, the present data suggest that the psychosexual development of the male rat also requires either prenatal estradiol or perinatal testosterone. [less ▲]

A semiautomated test apparatus for studying partner preference behavior in the rat.

in Physiology & Behavior (1994), 56(3), 597-601

A semiautomated three-compartment box (3CB) for studying partner preference behavior of rats is described. This apparatus automatically records the rat's time spent in each compartment, as well as the ... [more ▼]

A semiautomated three-compartment box (3CB) for studying partner preference behavior of rats is described. This apparatus automatically records the rat's time spent in each compartment, as well as the locomotor activity (i.e., the number of visits an animal pays to each compartment). Software was developed for calculating partner preference scores. Behavioral testing in the semiautomated 3CB, which is a modification of an earlier version, is less time consuming and less laborious. Three 3CBs can be observed simultaneously by two trained observers, and the behavioral interactions of three experimental animals with the stimulus animals can be observed and scored by hand. The use of the new apparatus was validated by studying adult partner preference behavior of neonatally ATD-treated male rats. The collected data fully corroborate previous results, obtained in the earlier version of the 3CB, again revealing the behavioral bisexual nature of these ATD males. A new finding was the much higher locomotor activity of the ATD males compared to controls. [less ▲]

Androgen and Estrogen Action in the Preoptic Area and Activation of Copulatory Behavior in Quail

in Physiology & Behavior (1990), 48(5), 599-609

The sites of androgen and estrogen action on sexual behavior were studied in the preoptic area of castrated male Japanese quail by stereotaxic implantation of hormones, antihormones and metabolism ... [more ▼]

The sites of androgen and estrogen action on sexual behavior were studied in the preoptic area of castrated male Japanese quail by stereotaxic implantation of hormones, antihormones and metabolism inhibitors. The first experiment demonstrated that bilateral implantation of the aromatase inhibitor, androstatrienedione (ATD), in the sexually dimorphic nucleus (POM) of the preoptic area can completely suppress the behavioral activation produced by a systemic treatment with testosterone. The effects of ATD were only observed if the implants were located in the POM. In the second experiment, implants in the POM of the synthetic estrogen, diethylstilbestrol, restored copulatory behavior in castrated males while implants of the synthetic nonaromatizable androgen, methyltrienolone, were almost ineffective. During the third experiment, the activating effects of a systemic treatment with testosterone were blocked by stereotaxic implants in the POM of the antiestrogen, tamoxifen, or the antiandrogen, flutamide. The effects of tamoxifen were more pronounced than those of flutamide. In addition, tamoxifen was active in all parts of the POM while a behavioral inhibition was observed only for flutamide implants which were located in the caudal part of the nucleus. Taken together, these results demonstrate that the sexually dimorphic POM is the area where the behaviorally active estrogenic metabolites of T have to be produced. The estradiol derived from T aromatization presumably acts within the POM to activate copulation as demonstrated by the effectiveness of DES implanted in this region. Androgens also have a direct action on sexual behavior as suggested by the partial inhibition observed in flutamide-treated birds. It is, however, suggested that androgens and estrogens do not act in the same brain area to activate behavior. [less ▲]

Effects of metabolism inhibitors, antiestrogens and antiandrogens on the androgen and estrogen induced sexual behavior in Japanese quail.

in Physiology & Behavior (1986), 38(4), 581-91

The relative contribution of androgenic and estrogenic metabolites of testosterone to the activation of sexual behavior was studied in Japanese quail by using inhibitors of testosterone metabolism ... [more ▼]

The relative contribution of androgenic and estrogenic metabolites of testosterone to the activation of sexual behavior was studied in Japanese quail by using inhibitors of testosterone metabolism, antiestrogens and antiandrogens. These compounds were tested in castrated birds whose sexual behavior had been activated by silastic implants of testosterone (T) or daily injections of testosterone propionate (TP) or diethylstilboestrol (DES). The aromatase inhibitor ATD only depressed T-induced behavior when injected at high doses and the 5 alpha-reductase inhibitor, 4MA was inactive in this respect. The antiestrogens, tamoxifen (TAM) and nitromifene citrate (CI-628) strongly depressed sexual behavior but they also drastically reduced the crowing behavior which is typically androgen-dependent which throws some doubts on the specificity of their action. The antiandrogens, flutamide and cyproterone acetate (CA), only had limited inhibitory effects on the copulatory behavior but similarly decreased only marginally the crowing. As they strongly depressed the cloacal gland growth, it can be ascertained that they were injected in sufficient amounts and their lack of action on crowing questions the ability of these compounds to inhibit brain processes even when they are androgen-dependent. Taken together with the results of previous experiments which tested the behavioral effects of the testosterone metabolites, the present data confirm the implication of both androgenic and estrogenic metabolites of testosterone in the activation of behavior. Their interaction remains, however, poorly defined and its understanding will probably require the identification of the biochemical processes which in the brain mediate the behavior. [less ▲]

Testosterone metabolism and testosterone-dependent characteristics in Japanese quail.

in Physiology & Behavior (1984), 33(5), 817-23

In 2 independent experiments, we measured and correlated in maturing male Japanese quail the individual variations in sexual and aggressive behavior, cloacal gland size, testes weight, plasma testosterone ... [more ▼]

In 2 independent experiments, we measured and correlated in maturing male Japanese quail the individual variations in sexual and aggressive behavior, cloacal gland size, testes weight, plasma testosterone concentrations and intracellular testosterone metabolism by hypothalamus and cloacal gland. Cloacal gland area was only weakly related to plasma testosterone levels but was positively correlated with the production of active androgenic metabolites and negatively related to the production of 5 beta-reduced androgens (inactive) in the glandular tissue. Several measures of behavior were correlated with aspects of the testosterone metabolism in the anterior hypothalamus. In both experiments, the behavior of the birds was also strongly correlated with their testes weight and their cloacal gland area but weakly or not at all with their plasma testosterone levels. These studies suggest that testosterone metabolism is involved in the control of hormone action in maturing animals. [less ▲]