Intraneuronal Convergence of Tactile and Hormonal Stimuli Associated with Female Reproduction in Rats

Stimulation of the vagina and cervix, by mating or manual probing, elicits many behavioral and endocrine changes associated with female reproduction in rats. We and others have identified neurons in the medial preoptic area, medial division of the bed nucleus of the stria terminalis, posterodorsal portion of the medial amygdala, ventromedial hypothalamus, dorsomedial hypothalamus and midbrain central gray that increase Fos expression in response to vaginal-cervical stimulation (VCS). In the present study, we used a double-label immunofluorescent technique to determine if any of these VCS-responsive neurons also contained estrogen receptor-immunoreactivity. We found that over 80% of the VCS-induced Fos-IR neurons in the medial division of the bed nucleus of the stria terminalis also contained estrogen receptor-immunoreactivity. Furthermore, high percentages of VCS-responsive neurons in the medial preoptic area, posterodorsal medial amygdala, ventromedial hypothalamus and midbrain central gray contained estrogen receptor-immunoreactivity as well. These results suggest that sensory and hormonal information associated with female reproduction converge on specific populations of neurons and may be integrated at the molecular level within these neurons.     

Estradiol and progesterone influence the response of ventromedial hypothalamic neurons to tactile stimuli associated with female reproduction

Stimulation of the vagina and cervix, provided by the male during copulation or manually with a probe, causes many behavioral and endocrine changes associated with female reproduction in rats. Previously, we found that vaginal-cervical stimulation (VCS), by mating or manual probing, increases the expression of Fos-immunoreactivity (Fos-IR) in discrete populations of neurons in the preoptic area, mediobasal hypothalamus and midbrain, suggesting that these neurons respond to VCS. The purpose of the present study was to determine if hormonal priming would increase the number of Fos-IR cells following VCS. Contrary to our hypothesis, in Experiment 1 priming animals with a behaviorally effective dose of 17β-estradiol benzoate followed 48 h later by progesterone caused a trend towards a decrease in the number of VCS-induced Fos-IR cells in the ventromedial hypothalamus. In Experiment 2, which was done to confirm this decrease in VCS-induced Fos-IR neurons by hormones, this effect was found to be statistically significant. Furthermore, this hormone-induced decrease in VCS-responsive cells was localized to the ventromedial nucleus of the hypothalamus, an area rich in estrogen and progestin receptors. No effects of hormone treatment on VCS-induced Fos-IR were observed in any other brain regions analyzed. These findings suggest that steroid hormones may elicit some of their effects on female reproductive behavior and physiology by altering the responsiveness of ventromedial nucleus neurons to vaginal-cervical stimulation.     

Efferent Projections from the Ovarian Steroid Receptor-Containing Area of the Ventrolateral Hypothalamus in Female Guinea Pigs

The ventrolateral hypothalamus (VLH) in female guinea pigs includes a subset of neurons which contain estrogen and progestin receptors, and which are implicated in the regulation of female sexual behavior by steroid hormones. However, little is known about where these neurons project, and consequently which other brain areas are involved in sexual behavior in female guinea pigs. The anterograde tracer Phaseolus vulgaris -Leucoagglutinin was used to label efferents from the ovarian steroid receptor-containing part of the VLH. To identify the correct placement of the tracer specifically within the group of neurons containing estrogen receptors, medial hypothalamic sections were also immunostained for estrogen receptors. Forebrain areas receiving dense projections from the ventrolateral hypothalamus included the bed nucleus of the stria terminalis, medial preoptic area, anterior hypothalamic area, anterior ventromedial hypothalamus, and caudal ventrolateral hypothalamus. The midbrain central gray was also heavily labeled. Moderate innervation was observed in the forebrain in the basolateral amygdala, medial preoptic nucleus, lateroanterior hypothalamic nucleus, dorsal hypothalamic areas, posterior hypothalamus, zona incerta, and in the midbrain interspersed among the central and lateral tegmental tracts. The major efferent pathways from the VLH appeared to travel rostrally through the mediobasal hypothalamus and preoptic area, and caudally via the medial thalamic nuclei and periventricular fiber system. These findings are similar to those of previous studies tracing the efferents from the ventromedial nucleus in rats and from the lateral hypothalamus in guinea pigs. Many of these areas that receive input from the steroid receptor rich area within the VLH are likely to be involved in the regulation of female sexual behavior.     

Reproductively-Relevant Stimuli Induce Fos-Immunoreactivity within Progestin Receptor-Containing Neurons in Localized Regions of Female Rat Forebrain

An experiment was conducted to determine if neurons that respond to stimuli associated with mating in female brain also contain progestin receptors. We found that a portion of the neurons that respond to stimuli associated with mating also contains progestin receptors. While the appropriate hormonal conditions are important for sexual receptivity, somatosensory information provided by the male also influences sexual behavior. One important stimulus provided by the male during copulation is vaginal-cervical stimulation (VCS). VCS has been shown to elicit many different behavioral and endocrine changes in female rats, such as increases in lordosis, pseudopregnancy, and termination of sexual receptivity. VCS also increases the expression of the immediate early gene product, Fos, in areas associated with reproduction. A portion of the neurons responding to VCS with increased Fos-immunoreactivity (Fos-IR) in female rat forebrain also contains estrogen receptors, illustrating that hormonal and mating-stimuli converge in a population of cells. As progesterone also plays an important role in female sex behavior, it is important to determine if some of the neurons also integrate information concerning serum progesterone levels and social interactions. Thus, we used a dual immunofluorescent technique to label both Fos-IR and progestin receptor-immunoreactivity (PR-IR) in the brains of estradiol-primed, ovariectomized female rats following VCS manually applied by the experimenter. Many of the neurons that respond to VCS with increased Fos-IR within the medial preoptic area, the arcuate nucleus, and the progestin receptor-rich areas of the rostral and caudal ventromedial nucleus of the hypothalamus also contain PR-IR.     

Septal complex of the telencephalon of lizards: III. Efferent connections and general discussion

The projections of the septum of the lizard Podarcis hispanica (Lacertidae) were studied by combining retrograde and anterograde neuroanatomical tracing. The results confirm the classification of septal nuclei into three main divisions. The nuclei composing the central septal division (anterior, lateral, medial, dorsolateral, and ventrolateral nuclei) displayed differential projections to the basal telencephalon, preoptic and anterior hypothalamus, lateral hypothalamic area, dorsal hypothalamus, mammillary complex, dorsomedial anterior thalamus, ventral tegmental area, interpeduncular nucleus, raphe nucleus, torus semicircularis pars laminaris, reptilian A8 nucleus/ substantia nigra and central gray. For instance, only the medial septal nucleus projected substantially to the thalamus whereas the anterior septum was the only nucleus projecting to the caudal midbrain including the central gray. The anterior and lateral septal nuclei also differ in the way in which their projection to the preoptic hypothalamus terminated. The midline septal division is composed of the dorsal septal nucleus, nucleus septalis impar and nucleus of the posterior pallial commissure. The latter two nuclei projected to the lateral habenula and, at least the nucleus of the posterior pallial commissure, to the mammillary complex. The dorsal septal nucleus projected to the preoptic and periventricular hypothalamus and the anterior thalamus, but its central part seemed to project to the caudal midbrain (up to the midbrain central gray). Finally, the ventromedial septal division (ventromedial septal nucleus) showed a massive projection to the anterior and the lateral tuberomammillary hypothalamus. Data on the connections of the septum of P. hispanica and Gecko gekko are discussed from a comparative point of view and used for better understanding of the functional anatomy of the tetrapodian septum. J. Comp. Neurol. 401:525–548, 1998. © 1998 Wiley-Liss, Inc.     

A subset of progesterone target neurons have axonal projections to the midbrain

Progestin-concentrating neurons in the preoptic area and hypothalamus that project to the midbrain in the female rat were identified using the combined steroid hormone autoradiography-retrograde axonal tracing technique. Progesterone target neurons were most abundant in the periventricular preoptic area and the medial preoptic nucleus, and in the ventromedial and arcuate nuclei of the hypothalamus. In the medial preoptic area as a whole, about 14% of the progestin-concentrating cells were afferent to the midbrain. More specifically, 23% of medial preoptic nucleus progesterone target neurons communicated directly with midbrain cell groups, whereas a much smaller percentage (2%) of periventricular preoptic target neurons projected to the midbrain. In the medial basal hypothalamus as a whole, 11% of the progestin-concentrating cells detected sent axons to the midbrain. This proportion was slightly higher in the ventromedial nucleus (15%), and much lower in the arcuate nucleus (3%). In the dorsal and lateral hypothalamic areas, close to 30% of the progesterone target neurons sent axons to the midbrain, although the total number and density of target cells in the two latter areas was low. These data support the idea that transduction by forebrain target neurons of the progesterone signal into altered synaptic transmission in the midbrain is one route through which progesterone can influence a variety of behaviors.     

Sex differences in cytosolic progestin receptors in microdissected regions of the hypothalamus/preoptic area of guinea pigs

Cytosolic progestin receptors (CPRs) were measured in microdissected nuclei of the hypothalamus and preoptic area of male and female guinea pigs. Adult gonadectomized animals were given 3 daily injections of 20 micrograms/day estradiol benzoate (EB) or oil vehicle. 24 h later, animals were sacrificed and cytosolic progestin receptors were measured using the synthetic progestin 3H-R5020. CPR levels did not differ significantly between oil treated males and oil treated females in any brain areas examined. With EB treatment, males showed significant increases in CPRs in most of the brain areas in which females showed increases, i.e. in the medial preoptic area, the periventricular part of the preoptic area, the periventricular part of the anterior hypothalamus, the ventromedial nucleus of the hypothalamus, the periventricular part of the medial hypothalamus and the arcuate-median eminence. However, EB treated males showed significantly lower CPR levels than EB treated females in both the periventricular part of the preoptic area and the periventricular part of the medial hypothalamus.     

Organization of projections from the dorsomedial nucleus of the hypothalamus: A PHA-L study in the rat

The axonal projections of the dorsomedial nucleus of the hypothalamus were investigated by using Phaseolous vulgaris-leucoagglutinin. The main conclusion of this work is that these projections are largely intrahypothalamic, with smaller components directed toward the brainstem and telencephalon. Although the intrahypothalamic pathways are very complex and intermix at various levels, we conclude that dorsomedial nucleus outputs follow three distinct ascending pathways: periventricular, coursing through the hypothalamic periventricular zone; ventral, traveling beneath the medial zone; and lateral, ascending in medial parts of the lateral hypothalamic area. Within the hypothalamus, the most densely innervated areas are the paraventricular nucleus, other dorsal regions of the periventricular zone, the preoptic suprachiasmatic nucleus, and the parastrial nucleus. Other significant terminal fields include the median preoptic, anteroventral periventricular, lateral part of the medial preoptic, and anteroventral preoptic nuclei; and the retrochiasmatic (including perisuprachiasmatic) area. Descending projections follow two pathways that also converge at various levels: a dorsal pathway in the midbrain periventricular system travels through, and primarily innervates, the periaqueductal and pontine gray, and a ventral pathway extends through ventromedial regions of the brainstem. Although sparse, fibers in the later pathway can be traced as far caudally as the nucleus of the solitary tract. The results are discussed relative to the pathways and properties of nearby hypothalamic medial zone nuclei. Dorsomedial nucleus projections are similar to certain other nuclei (e.g., anteroventral periventricular and parastrial) with predominantly intrahypothalamic projections, and different from those arising in the medial zone nuclei (medial preoptic, anterior hypothalamic, ventromedial, and mammillary). © 1996 Wiley-Liss, Inc.     

The organization of the hypothalamic pathways mediating affective defense behavior in the cat

The purpose of this study was to describe the hypothalamic pathways which mediate affective defense in the cat utilizing the methods of [14C]2-deoxyglucose (2-DG) and [3H]leucine radioautography in concert with the technique of electrical brain stimulation. The feline affective defense response, characterized by pupillary dilatation, piloerection, ear retraction, hissing, growling and striking with the forepaws, was elicited consistently by stimulation of sites within the ventromedial hypothalamus and anterior aspect of the medial hypothalamus. In one series of experiments, 2-DG autoradiography was employed to describe the brain regions activated following stimulation of sites in the region of the ventromedial hypothalamus from which affective defense had been elicited. Ventromedial hypothalamic stimulation produced activation primarily in forebrain regions situated rostral to the level of the stimulating electrode. These structures included principally the anteromedial hypothalamus and medial preoptic area, as well as the bed nuclei of the stria terminalis and anterior commissure, diagonal band and lateral septal area. The caudal extent of activation included only the dorsal and perifornical hypothalamus at the level of the stimulation site. In a second series of experiments, affective defense sites in the anteromedial hypothalamus were stimulated and the regional distribution of 2-DG label was identified. In contrast to the results obtained from ventromedial hypothalamic stimulation, these experiments revealed a marked descending distribution of label within the posterior hypothalamus, midbrain central gray and ventral tegmental area. Results obtained from studies in which tritiated amino acids were injected into affective defense sites in both the ventromedial nucleus and anteromedial hypothalamus confirmed the general findings observed with 2-DG autoradiography. From these observations, we have concluded that the organization of the pathway mediating affective defense behavior from the ventromedial hypothalamus to the midbrain involves an initial synapse within the region of the anteromedial hypothalamus and a second synapse in the midbrain central gray substance. The significance of the anteromedial hypothalamus for the expression of affective defense behavior was considered in the Discussion.     

A progestin antagonist blocks vaginocervical stimulation-induced fos expression in neurones containing progestin receptors in the rostral medial preoptic area

Vaginocervical stimulation (VCS) has a variety of effects on the brain, physiology and behaviour. Previous work demonstrated that a progestin antagonist blocked neuronal response to VCS (i.e. Fos expression) in the absence of progesterone in some neurones, and suggested that some of the effects of VCS on the brain are mediated by ligand-independent activation of progestin receptors (PRs). Although it had been reported previously that some of the cells in which VCS induces Fos expression also contain PRs, it had not been determined if a progestin antagonist blocked Fos expression in these particular neurones. The purpose of this experiment was to determine if a progestin antagonist decreases Fos expression specifically in cells that also express PRs in the preoptic area and ventromedial hypothalamus. As has been shown previously, VCS increased Fos-immunoreactive (ir) expression in the particular areas studied. In the rostral medial preoptic area, VCS increased Fos expression in cells that coexpressed PRs, as well as in cells that do not. However, in the caudal medial preoptic area, VCS only increased Fos expression in cells that did not coexpress PRs. Injection of the progestin antagonist, RU 486, decreased Fos expression in the rostral, but not caudal medial preoptic area, and it decreased Fos expression only in cells that coexpressed PR-ir. In contrast to a previous report, in the present study, the progestin antagonist did not inhibit VCS-induced Fos expression in the ventromedial hypothalamic area. The results of this experiment suggest that the progestin antagonist inhibits VCS-induced Fos expression in some neurones by blocking PRs, and they provide further support for the idea that VCS influences neuronal response in some cells by ligand-independent activation of PRs in those cells.     

Efferents from the medial anterior hypothalamic area in the guinea pig

Medial anterior hypothalamic connections were studied with H³-proline and autoradiography. Most of the axons projected to other hypothalamic nuclei. The major pathways were found ventral medial to the fornix and in the periventricular tract. Substantial projections were apparent in the ventromedial and dorsomedial nuclei with less label in the arcuate nucleus. The dorsal premammillary nuclei were labeled bilaterally, particularly with more caudal injections of anterior hypothalamus. Efferents were evident in the posterior hypothalamus and continued into the central gray of the midbrain. Labeled fibers reached the ventral tegmental area and in the reticular formation were traced only through pons. Rostral projections were to the medial and lateral preoptic areas and ventral lateral septum. The bed nucleus of stria terminalis was labeled and a very few fibers reached the medial amygdaloid nucleus. The periventricular nucleus of thalamus was labeled.     

Immunocytochemical localization and quantitation of estrogen-binding cells in the male and female (virgin, pregnant, lactating) mouse brain

Estrogen-binding cells in the brains of male, virgin, pregnant, and lactating female mice were localized and quantified using an immunocytochemical technique. Nuclear estrogen-receptors were detected in cells of the midbrain periventricular gray, the cortical and medial amygdaloid nucleus, the arcuate nucleus and ventromedial nucleus of the hypothalamus, the anterior hypothalamic area and the preoptic area in animals of all 4 experimental groups. In virgin females, immunostaining was also seen in the hippocampus, the entorhinal and piriform cortex and in the septal nuclei. In pregnant females the anterior amygdaloid area and the bed nucleus of the stria terminalis were labelled additionally. After the first 5 days of lactation, estrogen-binding cells could no longer be detected in the hippocampus, entorhinal and piriform cortex and anterior amygdaloid area. These apparent qualitative differences in the pattern of estrogen-receptor immunostaining among the experimental groups are further accentuated by significant quantitative differences in the absolute numbers and relative densities of labelled cells in a given nucleus. Pregnant females have the highest numbers of estrogen-binding cells in many nuclei, whereas lactating females have the highest densities of labelled cells. These differences suggest a dynamic regulation of the number and distribution of estrogen-target cells in the respective brain areas initiated by, or as a result of hormonal states of the animals. Functional implications are discussed.     

Efferent connections of the anterior hypothalamic nucleus: a biocytin study in the cat

The efferent connections of the anterior hypothalamic nucleus (AH) were examined using biocytin as anterograde tracer in the cat. The results provide several new findings in addition to confirming earlier observations. In the hypothalamus, the AH projections terminated mainly in the medial regions which are related to the defensive, reproductive and feeding behaviors, and autonomic functions. Moreover, we found dense patches of the AH terminals in the medial preoptic area and ventromedial hypothalamic nucleus, which suggests the existence of modular connections between sub-regions of each nucleus. In addition, the AH projected to regions which may be related to the emotional and autonomic responses, i.e., such regions in the amygdala, midline thalamus, septum, subthalamus, and midbrain. The data suggest that the AH may play an important role in the autonomic functions and behaviors between animals, and thus may play a key role in the defensive behavior elicited in the medial preoptic area and ventromedial hypothalamic nucleus.     

Identification of medial preoptic neurons that concentrate estradiol and project to the midbrain in the rat

Fluorescent dye retrograde tracing was combined with steroid hormone autoradiography to study the midbrain projections of the estrogen-concentrating neurons in the preoptic region of the rat brain. Microinjections of the dyes DAPI, true blue, or a mixture of DAPI and primuline were made into the ventral tegmental area and into the midbrain central gray of ovariectomized, adrenalectomized 2-3-month-old female rats; 3 or 4 days later these animals were injected with [3H]estradiol; the brains were then processed for autoradiography. After exposures of from 3 to 12 months, the autoradiograms were developed and examined for reduced silver grains under cell nuclei (indicating binding of [3H]estradiol) and retrogradely transported fluorescent dye in the cytoplasm (indicating an efferent projection to the midbrain). Numerous [3H]estradiol-concentrating neurons in the medial preoptic region were found to send their axons to the medial midbrain. The largest numbers of estrogen target neurons that were afferent to the ventral tegmental area and to the midbrain central gray were found in the medial preoptic nucleus, in the surrounding medial preoptic area, and in the ventral bed nucleus of the stria terminalis. Double-labeled neurons were also identified in the preoptic suprachiasmatic area, in the lateral preoptic area, and in the rostral anterior hypothalamic area. Thus, a subset of the gonadal steroid target cells of the preoptic region have long projections to the medial midbrain, and a subset of the medial preoptic neurons that project to the ventral tegmental area and to the midbrain central gray concentrate estrogen. Behaviors (for example, maternal behavior, male copulatory behavior, and wheel-running) that are regulated by estrogen action in the medial preoptic region may be controlled by the direct estrogen-sensitive pathway to the medial midbrain revealed in this study.     

A C-2-Deoxyglucose analysis of the neural pathways of the limbic forebrain in the rat: II. The hypothalamus

An attempt was made to characterize the nature of the functional organization of the hypothalamus by observing the patterns of uptake of ¹⁴C-2-deoxyglucose (2DG) following electrical stimulation of different regions within the preoptico-hypothalamus in the rat. The experimental paradigm consisted of electrical brain stimulation delivered continuously for periods of 30 sec on and 30 sec off for 45 minutes following injection of 2DG. Brains were removed and processed for autoradiography. Activation of the medial forebrain bundle was noted following stimulation of the nucleus accumbens and lateral preoptico-hypothalamus. Activated fibers could be followed only in a caudal direction through the medial forebrain bundle and into the ventral tegmental area as a result of nucleus accumbens stimulation. Stimulation of the lateral preoptic region or of the anterior half of lateral hypothalamus produced activation of the lateral septal nucleus, lateral habenular nucleus, perifornical region, midline thalamus and ventral tegmental area. Since stimulation of the perifornical hypothalamus significantly activated the rostro-caudal extent of the midbrain central gray, it is suggested that impulses from the lateral hypothalamus reach the lower brainstem via its connections with the perifornical hypothalamus. Ventromedial hypothalamic stimulation activated only the lateral septal nucleus, cortico-medial amygdala and medial preoptico-hypothalamus, while medial preoptico-hypothalamic stimulation resulted in increased 2DG uptake in the midbrain central gray, thus suggesting that medial hypothalamic impulses reach the brainstem by first ascending to the level of the preoptico-hypothalamus. Mammillary body stimulation orthodromically activated fibers in the mammillothalamic and mammillotegmental tracts and antidromically fibers in the fornix for a short distance.     

Sexual behavior in male rhesus monkeys elicited by electrical stimulation of preoptic and hypothalamic areas

Electrical stimulation of the preoptic area, lateral hypothalamus or dorsomedial nucleus of the hypothalamus (DMH) has produced sexual behavioral responses in 11 male rhesus monkeys. At a short latency following the onset of each train of stimulation, the stimulated males would mount estrogen-treated, receptive females. Quantitative measures of the elicited sexual behavior, in 4 males, were applied to describe differences between the effect of preoptic and DMH stimulation on male sexual performance. As compared to spontaneous sexual activity, stimulation of the DMH produced mounts of longer duration, with more thrusts per mount, higher thrusting rates and a greater number of ejaculations per test session; refractory periods between successive ejaculatory episodes were shortened as a result of stimulation-induced mounting behavior. Preoptic stimulation also induced mounts of longer than normal duration characterized by a slightly increased number of thrusts per mount. In contrast to DMH stimulus effects, however, thrusting rate was decreased significantly by preoptic stimulation and ejaculation did not occur even after multiple stimulus-induced mounts. Penile erections were elicited by stimulation of the anterior hypothalamus, ventromedial nucleus and the posterior hypothalamus in socially isolated or restrained males; however, stimulation of these same sites was ineffective for provoking sexual behavioral responses when tests were performed while the males were paired with receptive females.     

Age-related changes in cytoplasmic estradiol receptor concentrations in microdissected brain nuclei: Correlations with changes in steroid-induced sexual behavior

The purpose of this study was to: (1) determine at what age changes in cytoplasmic estradiol receptors are evident in specific microdissected brain areas of the female rat; (2) assess whether alterations parallel previous changes observed when large brain areas were used for determination of receptor concentrations; and (3) assess whether changes in cytoplasmic estradiol receptors are correlated with changes in steroid-mediated physiological functions.To assess the effects of age on cytoplasmic estradiol receptor concentrations, we used virgin female Sprague-Dawley rats at 3–4 months, 7–8 months and 10–11 months of age. They were ovariectomized 7–14 days prior to use to allow maximal translocation of receptors to the cytoplasm. The animals were anesthetized and perfused with a 10% (v/v) solution of dimethylsulfoxide to protect the receptor proteins from the effects of freezing. Brains were removed and frozen. This procedure of freezing the brains caused a minimal (15–18%) loss in the number of receptors and no change in the dissociation constant. Consecutive 300 μm sections were sliced and the following nuclei and brain areas were microdissected: bed nucleus of the stria terminalis, suprachiasmatic-preoptic area, medial preoptic nucleus, periventricular preoptic nucleus, periventricular anterior hypothalamic area, paraventricular nucleus, dorsomedial nucleus, ventromedial nucleus, arcuate-median eminence, medial amygdala, and cortical amygdala. The pituitary gland was also removed and analyzed. The cytoplasmic fraction from a tissue pool from 3 animals was prepared and aliquots were incubated with [³H]estradiol at a final concentration of 1.5 nM in the presence or abssence of 100-fold excess moxestrol. Receptor-bound [³H]estradiol was separated from free hormone by gel filtration. There was no difference in cytoplasmic estradiol receptor concentrations in any brain area in 7–8-month-old rats compared to 3–4-month-old rats. In marked contrast, by 10–11 months of age, there was a significant decrease in the number of cytoplasmic estradiol receptors in the suprachiasmatic-preoptic area and medial preoptic nucleus with a similar trend in the bed nucleus of the stria terminalis and periventricular preoptic nucleus. These brain areas are included in the grossly dissected preoptic area used in previous studies. We observed an unexpected decrease in the ventromedial nucleus, but no change in the dorsomedial nucleus, paraventricular nucleus, periventricular anterior hypothalamic area or arcuate-median eminence, areas included in the grossly dissected medial basal hypothalamus.Since the ventromedial nucleus is involved in steroid-induced reproductive behavior we examined whether or not the decrease in cytoplasmic estradiol receptors in this area is correlated with behavioral changes. Young (3–4 month) and middle-aged (10–11 month) rats were ovariectomized and 1–3 weeks later, they received Silastic capsules which produced physiological levels of plasma estradiol. Two days later, 4 h before testing, rats received subcutaneous injections of progesterone. Proceptive behavior, lordosis quotient and lordosis quality score were assessed. Middle-aged rats showed significant deficits in all aspects of mating behavior. The data demonstrate that by 10–11 months of age, rats exhibit decreased cytoplasmic estradiol receptor levels in components of the preoptic area. The use of microdissection methods allowed us to detect changes in a particular component of the medial basal hypothalamus, the ventromedial nucleus. This was correlated with deficits in estradiol-induced behavior. The data suggest that changes in estradiol receptors may affect the ability of aging rats to respond to estradiol and may be a contributing factor to the age-related transition to acyclicity and infertility.     

Metabolic mapping of the rat brain involved in thermoregulatory responses using the [C]2-deoxyglucose technique

The central nervous structures involved in thermoregulatory responses to thermal stimulation of the preoptic/anterior hypothalamic region were investigated in conscious, unrestrained rats by means of the 2-deoxy-d-[¹⁴C]glucose autoradiographic technique. Significant activation in metabolic activity was observed in the medial preoptic area, medial forebrain bundle, anterior part of ventromedial hypothalamus, anteroventral thalamus, dorsomedial thalamus, basal ganglia, pars compacta of substantia nigra, red nucleus and the reticular formation.     

An enzyme tracer study of the organization of the somatic motor center for the innervation of different muscles of the tongue: Evidence for two sources

Autoradiography was used to localize target cells for ³H-testosterone or its labeled metabolites in the brain of the rhesus monkey. Two castrated males were injected intravenously with ³H-testosterone (2 mCi/monkey) and were killed 1 hour later. In both animals, neurons that concentrated radioactivity in their nuclei were located in a well-circumscribed system that included the bed nucleus (n.) of the stria terminalis, medial preoptic n., suprachiasmatic preoptic n., anterior hypothalamic area, ventromedial hypothalamic n., cortical, medial, and basal accessory amygdaloid n., mesencephalic reticular n., and periaqueductal gray matter. In contrast to reports in some nonprimate mammalian species, little or no cellular labeling was observed in the lateral septum, arcuate n.-median eminence, motor nuclei of cranial nerves, or spinal cord.     

Differential effects of progesterone and genital stimulation on sequential inhibition of estrous behavior and progesterone receptor expression in the rat brain

The effect of genital stimulation, either by vaginocervical stimulation (VCS) using a calibrated vaginal probe combined with manual flank stimulation (FS), or by mounts performed by the male, on the hypothalamus and preoptic area concentration of the progesterone receptors A (PR-A) and B (PR-B) was assessed in ovariectomized (ovx) estrogen-primed rats. VCS/FS or stimulation provided by male mounts, even without intromission, significantly decreased PR-B concentration in the hypoythalamus. Down regulation of PR produced by genital stimulation was quantitatively similar to that elicited by progesterone (P) administration. Bilateral or unilateral transection of the pelvic or the pudendal nerves prevented down regulation elicited by VCS/FS. Repeated VCS/FS elicited lordosis behavior in most ovx estrogen primed rats, but the lordosis intensity was lower than that observed in response to P. P administered to ovx estrogen primed rats, induced sequential inhibition, i.e., failure to display estrous behavior in response to a second P injection (24h after the initial P injection). VCS/FS failed to elicit sequential inhibition, since rats responded with normal estrous behavior to the second injection of P. This suggests that down regulation by VCS, by contrast with P, failed to inhibit the subpopulation of PR involved in the facilitation of estrous behavior by P.