Perinatal administration of diazepam alters sexual dimorphism in the rat accessory olfactory bulb.

The present study examines the effects of pre and/or early postnatal administration of diazepam on the mitral cell and on the light and dark granule cell populations in the sexually dimorphic accessory olfactory bulb of the rat. Quantitative differences related to sex were observed in the numbers of the three types of neurons, with vehicle males showing greater numbers of cells than vehicle females. The number of mitral cells in males decreased to the levels shown by female rats following prenatal and pre-postnatal diazepam treatments, whereas the DZ treatments did not affect the females. In addition, the diazepam administration during the prenatal, postnatal and pre-postnatal periods decreased the numbers of both light and dark granule cells in males, while these two granule cell subpopulations were not affected in diazepam treated females. These results indicate that perinatal administration of diazepam can alter the sexual dimorphism in the accessory olfactory bulb and that the GABAA/benzodiazepine receptor complex is involved in the sexual differentiation this part of the brain.

Effects of perinatal diazepam exposure on the sexually dimorphic rat locus coeruleus.

Diazepam (DZ) administration over prenatal, postnatal, and pre plus postnatal periods altered the normal expression of the morphological sex differences of the LC. Males were affected only by the prenatal exposure and the effect of this exposure produced an increase in the volume and neuron number of male's LC. By contrast, females were affected by both pre and postnatal treatments and the effect of this exposure resulted in a decrease in the volume and neuron number of female's LC. However, pre plus postnatal treatment did not affect female's LC.

Early postnatal estrogen organizes sex differences in the extinction of a CRF running response.

In the present study the organizational effects of sex steroids on the sexually dimorphic extinction of a continuously food-rewarded running response were investigated. Gonadally intact female rats neonatally treated from day 1 to day 8 of the postnatal life with estradiol benzoate (EB), dihydrotestosterone (DHT) or vehicle, and males treated in the same period with the antiandrogen ciproterone acetate (AC), the estrogen antagonist tamoxifen (TX) or vehicle were studied in adulthood during the acquisition and extinction phases of the response in a short and narrow runway. No difference in performance between groups was obtained in the response acquisition. However, during extinction control males extinguished faster than control females. DHT treatment to females and neonatal CA administration to males had no effect on the expression of sexual dimorphism. Conversely, TX administration to the males increased male's resistance to extinction at the levels shown by control or DHT females, whereas the females treated with EB exhibited similar extinction rates to those observed in nonhormonal treated or CA males. This finding suggests that the organizational effect of testosterone on the sexually dimorphic behavior studied in the present report are mediated by testosterone conversion to estradiol throughout the aromatization pathway in the brain.

Postnatal administration of dihydrotestosterone to the male rat abolishes sexual dimorphism in the accessory olfactory bulb: a volumetric study.

The regulatory action of the non-aromatizable androgen dihydrotestosterone (DHT) on sexual differentiation of the volume of the rat accessory olfactory bulb (AOB) was studied. Postnatal treatment with DHT (180 micrograms/day) carried out daily between days 6 and 20 produced a drastic reduction in overall AOB size and that of its constituent neural layers in genetic males with respect to intact and control males. The volumetric measures found in DHT-treated males did not differ from those shown by the intact females. These results, which indicate a demasculinization and a feminization of the AOB volume in gonadally intact male rats induced by DHT, are discussed in relation to the presumably regulatory role of DHT on neuron populations during the sexual organizational process of the brain.

Effects of early postnatal sex steroids on acquisition and extinction of a continuously reinforced lever-pressing response.

The effects of early postnatal dihydrotestosterone (DHT) and estradiol on the sexually dimorphic continuously reinforced lever-pressing response were investigated. 90-day-old male rats postnatally treated (during the first eight days of postnatal life) with cyproterone acetate (CA), tamoxifen (TX) or vehicle, and 90-day-old females treated with estradiol benzoate (EB), DHT or vehicle in the same postnatal period, were studied during the acquisition and extinction of the continuously reinforced lever-pressing response using a free-operant procedure. During acquisition, the control males made more responses per minute than the control females, and also reached the extinction criterion significantly sooner than the females. CA treatment impaired the male's performance at the levels of that shown by females, whereas TX treatment affected neither acquisition nor extinction. Inversely, in both experimental phases females treated with DHT performed like control females, whereas the acquisition and extinction performances of the EB-females were similar to those obtained in the control or TX male groups.

Female's DHT controls sex differences in the rat bed nucleus of the accessory olfactory tract.

In the present study the regulatory action of the non-aromatic androgen dihydrotestoterone (DHT) on the volume of the sexually dimorphic bed nucleus of the accessory olfactory tract (BAOT) was investigated. Postnatal treatment with DHT (180 micrograms day-1) between days 6 and 20 (D6-D20) induced, in gonadally intact male rats, a drastic reduction in the overall volume to levels typical in control females. Conversely, the postnatal administration of the anti-androgen cyproterone acetate (CA) to the females from D6-D20 produced an increment in the BAOT volume not dissimilar to that found in control males. These findings reveal that sexual organization in this vomeronasal structure is dependent on the presence of DHT in females during postnatal development.

Early postnatal diazepam exposure alters sex differences in the rat brain.

The volume and neuron number of the sexually dimorphic accessory olfactory bulb and locus coeruleus are altered by early postnatal exposure (from the day of birth to postnatal day 16) to diazepam. After diazepam treatment, both volume and neuron number were decreased in the male accessory olfactory bulb and in the female locus coeruleus. These results indicate that early postnatal diazepam administration can bear gender-dependent teratogenic effects upon sexually dimorphic nuclei and suggest that endogenous benzodiazepines may be involved in the sexual differentiation of the brain.

Effects of early postnatal gonadal steroids on extinction of a continuously food-rewarded running response.

In the present work the existence of sex differences (Experiment 1) on the acquisition and extinction of a continuously reinforced response in a short and narrow runway (100 x 9 x 10 cm) were investigated. In addition to the investigation of the basic sex differences in Experiment 1, the effect of postpuberal gonadectomy of male and female rats and the role of the early postnatal gonadal steroids on these situations were also examined in Experiments 2 and 3, respectively. In all experiments, no sex differences were found in acquisition. However, males extinguished faster than female rats. Gonadectomy of both sexes in adulthood, although it increases their latencies in acquisition, did not affect the differences between sexes during extinction. In contrast, in Experiment 3 female androgenization and male orchidectomy on day one after birth reversed the direction of sex differences found between control rats in the extinction period. Our findings suggests that the observed sex differences in extinction may be due to an underlying sexual dimorphism in the response inhibition process.

Effects of perinatal diazepam administration on two sexually dimorphic nonreproductive behaviors.

The effects of prenatal and/or early postnatal diazepam (DZ) administration on open field activity and continuously reinforced lever-pressing response were studied. Rat pups of both sexes were prenatally (during the last week of pregnancy) and/or postnatally (from the day of birth to day 16) daily exposed to a 2.5 mg/kg dose of DZ. At the age of 60 days all groups were tested in the open field for 5 consecutive days and thirty days later they were studied in a continuously reinforced lever-pressing situation during four consecutive days. In the open field test, females showed greater activity than males and prenatal and/or early postnatal DZ treatments did not alter this sexual dimorphism, although all treatments decreased the open field activity in both male and female 60-day-old rats. In the Skinner box, 90-day-old males presented higher rates of lever-pressing response than females, and only the early postnatal DZ treatment was effective in altering this sexual dimorphism, by decreasing the male's but not female's rates of response. These results are discussed in regard to the possible interaction between DZ and gonadal hormones during the early sexual differentiation period.

The distribution of glial fibrillary acidic protein in the adult rat brain is influenced by the neonatal levels of sex steroids.

Sex steroids during the perinatal period are able to modify the postnatal development of neurons within steroid-sensitive areas in the rat brain. This study was designed to test the possible influence of the early postnatal levels of sex steroids on the morphology of the astrocytes. The experimental manipulation of the neonatal levels of sex steroids was performed by the androgenization of females with a single injection of testosterone propionate and by the orchidectomy of males on the day of birth. Control females received a single injection of vehicle and control males were sham operated. All the animals were sacrificed at 3 months of age postnatally. The immunohistochemical distribution of the glial fibrillary acidic protein (GFAP), a marker of astrocytic filaments, was studied on coronal sections of the dorsal hippocampus, the globus pallidus and the hypothalamic arcuate nucleus. The number of GFAP immunoreactive cells, the number of GFAP immunoreactive primary processes per cell and the surface density of the GFAP immunoreactive material were evaluated. This morphometric evaluation revealed a decreased surface density of GFAP immunoreactive material in the hippocampus, globus pallidus and the ventral part of the arcuate nucleus of orchidectomized males when compared to control males. Sex differences in the distribution of GFAP immunoreactivity were detected in the hippocampus and globus pallidus. These differences were abolished by the androgenization of females. The number of GFAP immunoreactive cells was similar in all the experimental groups, indicating that the differences in surface density represent an effect of sex steroids on the growth of astrocytic processes rather than on the proliferation of astrocytes.

Effects of early postnatal gonadal steroids on acquisition and extinction of a single alternation response in discrete-trials lever pressing.

The present report studies the effect of sex on the acquisition and extinction of a single alternation schedule of reinforced (R) and nonreinforced (N) trials in a Skinner box. In addition to the investigation of the basic sex differences in Experiment 1, the effects of early gonadal steroids treatment and postpubertal gonadectomy of male and female rats were examined in Experiments 2 and 3, respectively. Both acquisition and extinction performances were evaluated by means of latency. In Experiment 1, males showed higher latencies on N trials and extinguished faster than female rats. In Experiment 2, female androgenization and male orchidectomy on day one after birth reversed the direction of the sex differences found in the previous experiment. However, postpubertal gonadectomy (Experiment 3) does not affect the performance of male and female rats.

Effects of sex steroids on the development of two granule cell subpopulations in the rat accessory olfactory bulb.

The effects of postnatal male castration on day 1 (D1) after birth and female androgenization on accessory olfactory bulb (AOB) light and dark granule cell populations were studied. Control males showed a greater number of both light and dark AOB granule cells than females. Postnatal treatment reversed these differences in the light granule cells. Female androgenization on D1 does not affect the number of AOB dark granule cells. However, male orchidectomy also on D1 significantly decreases the number of dark granule cells. Androgens injected into female rats are able to increase the number of AOB dark granule cells if they are administered on D14. This suggests a different critical period for the early effects of androgens on the dark granule cells with respect to light granule cells.

Effects of early postnatal gonadal steroids on the successive conditional discrimination reversal learning in the rat.

In the present study the existence of sex differences in the acquisition, retraining and reversal of a successive conditional discrimination learning (Experiment 1) and the role of the early postnatal gonadal steroids on these discrimination tasks (Experiment 2) were investigated. In Experiment 1 two groups of experimentally naive rats (males and females) were exposed to a black-white successive conditional discrimination task in a T-maze. No sex differences were found in the acquisition or retraining. However, in the reversal phase females made fewer errors and reached the discrimination criterion (90% of correct choices) sooner than males. In Experiment 2, the absence of sex differences in the acquisition or retraining phases and the existence of sexual dimorphism in the reversal period were confirmed. In addition, female androgenization and male orchidectomy, on day one after birth, reversed the direction of the sex differences found in the successive conditional discrimination reversal learning.