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Androgen and estrogen action in the preoptic area and activation of copulatory behavior in quail.

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.

Androgens↗

Neural transection between preoptic area and septum inhibits maternal behavior in female and male rats.

Artificially-induced maternal behavior was examined in inexperienced female and male rats following neural transection between the preoptic area and the septum. Anterior roof deafferentation (ARD) of the preoptic area (POA) was performed with an L-shaped microknife. Virgin female and male rats with or without ARD were exposed to the continuous presence of normal pups to induce maternal behavior 3 weeks after surgery. ARD resulted in a significant delay of the onset of maternal behavior in females and a lack of complete development of maternal behavior in males, compared with corresponding sham-operated and intact controls. The results indicate that neural substrates dorsal to the POA play an important role in modulating the expression of maternal behavior in the rat.

Animals↗

Nuclear localization of estrogen receptor-immunoreactivity in the preoptic area of female rats and its reduction by intraventricular colchicine treatment.

The subcellular localization of estrogen receptor (ER) was investigated in the preoptic area of ovariectomized female rats by electron microscopic immunohistochemistry, using a monoclonal antibody to ER. ER-immunoreactivity was localized in the nuclei of neurons of the periventricular preoptic nucleus (Pe) and the medial preoptic area (MPA). ER-immunoreactivity had a speckled pattern in the nucleus, but was not observed in the nucleolus or cytoplasm. After intraventricular colchicine treatment, ER-immunoreactivity within the nucleus was reduced drastically in neurons of the Pe and the MPA. The possible mechanism by which colchicine alters ER-immunoreactivity is mentioned.

Animals↗

Differential distribution of Fos expression within the male rat preoptic area and hypothalamus in response to physical vs. psychological stress.

Recent studies on stress-induced adrenal glucocorticoid secretion have demonstrated quantitatively different effects of individual stress stimuli on hormone release, suggesting that the hypothalamic-pituitary-adrenal axis exhibits discriminative, rather than ubiquitous responses to such challenges, particularly psychological vs. physical stressors. The immediate-early gene, cfos, is expressed by central nervous system neurons in response to numerous physiological stimuli, including stress. The following study investigated whether the distribution and/or intensity of immunolabeling for Fos in the preoptic area and hypothalamus differ after imposition of stressors of variable intensity. Groups of male rats were sacrificed by transcardial perfusion 2 h after (1) transfer to a novel environment (NE stress), (2) confinement within a restraint tube (REST stress), or (3) immobilization (IM) stress. Nonstressed controls remained undisturbed in their home cages. Whereas the NE-stress group exhibited Fos immunoreactivity (ir) only within anterior and lateroanterior hypothalamus, both physical stressors induced immunostaining for Fos in the lateral preoptic area, median preoptic, paraventricular, arcuate, dorsomedial hypothalamic nuclei, and lateral hypothalamus, while numbers of Fos-ir-positive neurons were generally greater in the IM vs. REST stress group. In the IM-stressed rats, additional Fos-ir was observed in the supraoptic and suprachiasmatic nuclei. These studies show that neurons expressing Fos-ir in response to the relatively mild stress of novel environment are distributed differently than those that are transcriptionally activated by more aversive stressors. Findings that Fos-ir occurs in several common sites following exposure to REST or IM stress suggest that local neuron populations may comprise a common neural pathway(s) that is activated by intense forms of stress.

Animals↗

Effects of lesions of the amygdala, preoptic area, and hypothalamus on estradiol-induced activity in the female rat.

Lesions of the anterior hypothalamic nucleus and the medial preoptic area sharply attenuated enhancement of wheel running by estradiol benzoate in ovariectomized female rats. Lesions of the corticomedial amygdala had no effect on this behavior. The hormonal effects on activity were largely independent of any changes in body weight. Results of this first experiment indicated that the anterior hypothalamic and medial preoptic areas are critically involved in the induction of activity by estradiol. However, this experiment provided no support for suggestions that the corticomedial amygdala inhibits those structures that mediate the estrogenic induction of activity. In the second experiment, food deprivation was used to stimulate activity. Results of this experiment suggested that the reduction in the ability of estradiol to induce activity following anterior hypothalamic and medial preoptic lesions does not reflect a general inability to become more active.

Amygdala↗

Sexual experience increases nitric oxide synthase in the medial preoptic area of male rats.

Nitric oxide in the medial preoptic area (MPOA) is important for the expression and sensitization of male sexual behavior. In this article, the authors report that repeated sexual experience (mating for 2 hr on each of 3 days) increased levels of nitric oxide synthase (NOS) in the MPOA of male rats, regardless of whether they mated on the day they were given an overdose of sodium phenobarbital. This effect resulted from the previous experience and not acute mating, as NOS was not increased 2 hr after the first mating in previously naive males. Experience-induced increases in NOS in the MPOA may be one mechanism through which sexual experience facilitates sexual behavior in male rats.

Analysis of Variance↗

An intracellular study of grafted and in situ preoptic area neurones in brain slices from normal and hypogonadal mice.

1. Intracellular recordings have been obtained from forty-one preoptic area (POA) neurones at times up to 14 months after they were grafted into the third ventricle of the mouse. Thirty-one neurones were in grafts from hypogonadal (hpg) mice in which a reversal of the hypogonadism was seen (responders), six were in grafts from hpg mice in which no such reversal occurred (non-responders) and four were in grafts from normal mice. 2. The grafted neurones had a mean resting potential (Em) of -57 mV, a mean apparent input resistance (Rm) of 136 M omega and a mean membrane time constant (tau m) of 7.7 ms. The slopes of the current-voltage (I-V) relations were linear. Approximately a quarter of neurones in responders fired action potentials spontaneously either singly or in bursts. Such activity could underlie the release of gonadotrophin hormone-releasing hormone (GnRH) which is known to occur from such grafts. 3. Two types of response were seen when these neurones were depolarized to firing threshold from Em, in one group a single action potential was discharged; in the other group one or more action potentials arising from a transient, slowly rising and falling depolarization (low-threshold response, LTR) was recorded. Some cells in the former category exhibited a LTR when depolarized from a potential more negative than Em. 4. The commonest response to stimulation of the median eminence in responders was an EPSP either alone or in combination with an IPSP. Antidromic action potentials were seen in four neurones and in two of these cells excitatory synaptic inputs could be demonstrated when the host hypothalamus adjacent to the graft was stimulated. It is suggested that these responses may represent activation of an afferent input from the host to neurones in the graft. 5. The morphology of neurones in POA grafts was determined by intrasomatic injection of horseradish peroxidase (HRP). A variety of profiles were seen and although some neurones extended over distances of up to 635 microns and branched extensively only one appeared to enter the host tissue at the ventrolateral edge of the graft. 6. A comparison was made between grafted POA neurones and cells in the medial preoptic area (MPOA), a region which constituted a significant component of the grafted tissue. No significant difference was noted between neurones in the graft and neurones in the MPOA in terms of their passive membrane properties. With regard to the active properties MPOA neurones could also be classified according to whether or not a LTR was elicited when the neurone was depolarized from Em. The major difference between the grafted neurones and those in the MPOA lay in the proportion of cells which exhibited a LTR under such conditions, being significantly greater in the latter group.

Animals↗

Hypothalamic regulation of mating-induced prolactin release. Effect of electrical stimulation of the medial preoptic area in conscious female rats.

Lesions of the medial preoptic area (MPOA) induce nocturnal prolactin surges similar to those initiated by cervical stimulation (CS). These same lesions can abolish diurnal prolactin surges previously initiated by CS. Based on these results the MPOA has been suggested to contain two functionally dissimilar sets of neurons, one inhibitory for the nocturnal surge and the other stimulatory for the diurnal surge. The present study sought to demonstrate the existence of these neural elements by electrically stimulating the MPOA of conscious ovariectomized female rats during those times of day when these neurons would be most active. Serial blood samples were collected via cannula before, during and after the stimulation. Stimulation of the MPOA (01.00-05.00 h) on day 2 after CS inhibited the nocturnal surge of prolactin while sham MPOA stimulation of CS females did not disturb the nocturnal surge. MPOA stimulation in non-CS females had no effect upon prolactin secretion. Application of MPOA stimulation (15.00-19.00 h) to CS females also suppressed the diurnal surge of prolactin. Sham-stimulated CS females, however, secreted a diurnal surge peaking at 17.00 h. Basal prolactin levels were unaffected by MPOA stimulation (15.00-19.00 h) in non-CS females. The results from these experiments suggest that the MPOA contains neurons inhibitory for both the nocturnal and diurnal prolactin surges. In a further attempt to show a stimulatory role for the MPOA in prolactin regulation, MPOA stimulation was applied (15.00-19.00 h) to pentobarbital anesthetized non-CS females. Pentobarbital treatment allowed the MPOA stimulation to trigger two prolactin peaks, one at 16.00 h and the other at 19.00 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ontogeny of a sexually dimorphic opioid system in the preoptic area of the rat.

A striking sexual dimorphism exists in the distribution of Met-enkephalin (m-ENK) immunoreactive fibers in the preoptic area of the rat brain. A dense plexus of m-ENK fibers, approximately 100 microns wide, is present in the periventricular part of the preoptic area (pePOA) in adult females, but not in males. In the present study, we have examined the time of first expression of this female-typical system during the course of normal brain development. The female-typical plexus of m-ENK fibers in the pePOA is not expressed prepubertally, but first becomes evident during the late peri-pubertal period (usually by 40 days of age). In adult females, the maintenance of immunohistochemically detectable levels of m-ENK in this fiber system is dependent upon the presence of gonadal steroids, especially estradiol. Therefore, we examined whether exposure of pre-pubertal females to estradiol would result in precocious expression of the m-ENK fiber plexus. The results of this experiment demonstrate that exposure to estradiol for 7 days induces the full expression of the m-ENK fiber system in the pePOA of prepubertal females, such that it was indistinguishable from that seen in mature animals. These results demonstrate that while the sexually dimorphic m-ENK system of the pePOA is not normally expressed prepubertally, the neural substrate is nevertheless in place and capable of being activated by exposure to exogenous estradiol.

Aging↗

Electrolytic lesions of the substantia innominata and lateral preoptic area attenuate the 'supersensitive' locomotor response to apomorphine resulting from denervation of the nucleus accumbens.

Apomorphine-stimulated locomotion in the rat is greatly enhanced following destruction of dopamine terminals in the nucleus accumbens (NA) with 6-hydroxydopamine (6-OHDA). While this augmented response is ascribed to the action of the dopamine stimulant apomorphine on supersensitive receptors within the NA, little is known regarding the mechanisms by which increased receptor stimulation within the NA influences lower motor circuitry to produce changes in locomotion. In this study, we examined apomorphine-stimulated locomotion in 6-OHDA-infused rats following electrolytic damage to the terminal region of first-order NA efferent fibers within the substantia innominata and lateral preoptic area. This damage greatly diminished the locomotor response to apomorphine in 6-OHDA-infused animals, but did not diminish locomotion in vehicle-infused animals. Destruction of dopamine terminals within the NA has also been reported to enhance the place-preference response to apomorphine in rats. Damage to the substantia innominata and lateral preoptic area significantly decreased the place-preference for apomorphine-paired environments in 6-OHDA-infused animals, but did not alter place-preference responses in vehicle-infused animals. Our results indicate that the efferent pathway from the NA to the substantia innominata and lateral preoptic area serves as an important output of mesolimbic activity into motor circuitry involved in the expression of apomorphine-stimulated locomotion and place-preference.

Animals↗

Estrogen-concentrating cells within cell groups of the medial preoptic area: sex differences and co-localization with galanin-immunoreactive cells.

Male and female rats have approximately equal numbers of estrogen(E)-concentrating cells within the medial preoptic area (MPOA). Several cell groups within this brain region are sexually dimorphic, however, and these groups may have sexually different numbers of E-containing cells; this, in turn, may reflect sex differences in neural-regulated functions. In order to study this possibility, the distribution of E-concentrating cells was determined using estrogen autoradiography. Except for the lateral portion of the medial preoptic nucleus (MPNl), the density of E-concentrating cells was 3-5-times higher within the most medially situated cell groups of the female than the male, i.e., within the anteroventral periventricular nucleus (AVPv), periventricular preoptic area (PVPO), medial portion of the medial preoptic nucleus (MPNm), and its central portion (MPNc). In addition, we determined whether E-concentrating cells also express the neuropeptide, galanin. An average of 13% of the E-concentrating cells were galanin positive, which represented 15% of the galanin-immunoreactive population. These results demonstrate a frank and dramatic sex difference in the distribution of E-concentrating cells within sexually dimorphic regions of the MPOA, and also suggest that an interaction between galanin and gonadal steroids may be an important means by which cells within the MPOA regulate reproductive function.

Animals↗

Nitric oxide synthase in the guinea pig preoptic area and hypothalamus: distribution, effect of estrogen, and colocalization with progesterone receptor.

Nitric oxide (NO) may function as an intercellular messenger in the hypothalamus and may play a role in the control of gonadotropin-releasing hormone (GnRH) secretion and sexual behavior. Progesterone also plays an important role in the regulation of reproductive functions. Recent experiments have shown that progesterone-induced sexual behavior in ovariectomized, estrogen-primed rats was caused by the release of NO from nitric oxide synthase (NOS)-containing neurons and the subsequent stimulation of the release of GnRH. To provide further neuroanatomical support for the role of NO in these gonadal steroid-dependent behavioral and physiological processes, we determined (1) the distribution of the nicotinamide-adenosine-dinucleotide phosphate-diaphorase (NADPHd) and NOS enzymes in the guinea pig preoptic area and hypothalamus, regions that contain steroid receptors; (2) the effect of estrogen on NADPHd activity in these regions; and (3) the neuroanatomical relationship between NOS and the progesterone receptor (PR). For this purpose, single-(NADPHd) and double- (NADPHd with NOS or NADPHd with PR or NOS with PR) staining techniques were applied to sections of brains of guinea pigs. The studies showed scattered NADPHd-positive neurons in most parts of the preoptic area and heavily stained cells in the hypothalamus. In these regions, the pattern and density of NOS immunoreactivity closely corresponded to the pattern of NADPHd staining. Quantitative analysis showed an increase in the number of NADPHd-positive neurons in the ventrolateral nucleus of ovariectomized animals primed with estradiol. Approximately 16% of the NOS-immunoreactive (IR) cells in the rostral preoptic area and 55% of NOS-IR cells in the ventrolateral nucleus displayed PR immunoreactivity. These results suggest that NOS may be regulated by gonadal steroids and provide neuroanatomical evidence that progesterone may exert its effect directly on more than half of NOS-synthesizing cells in the ventrolateral nucleus, a key region in the control of sexual behavior.

Animals↗

The distributions of apoptotic cells in the medial preoptic areas of male and female neonatal rats.

The medial preoptic area (MPA) of the hypothalamus of the rat contains two sexually dimorphic nuclei, the periventricular preoptic nucleus (PVpo) and the medial preoptic nucleus (MPN). To examine the relationship between sexual dimorphism and neuronal death, we examined the number of apoptotic cells in the subdivisions of the MPA in neonatal rats of postnatal days 1 (P1), 4 (P4), 7 (P7) and 14 (P14). Apoptotic cells in these areas were classified according to their progression into three stages. P1 and P4 rats contained many apoptotic cells in the subfield along the third ventricle, including the PVpo, and their number was significantly larger in P1 males: in particular, the number of early-stage cells was larger in males than females. The number of apoptotic cells in the MPN was increased in P4 and P7 rats, although no significant sexual differences were seen in the total number or in the number of each progressive stage of apoptotic cells. In P14 rats, very few apoptotic cells were seen in the MPA. Our data revealed that the distribution of apoptotic cells in the MPA of developing rats depends on the sexuality, subdivision of the area and postnatal period.

Animals↗

Effects of small medial preoptic area lesions on maternal behavior: retrieving and nest building in the rat.

Previous studies in rats have demonstrated that large lesions in the medial preoptic area (MPOA) disrupt all aspects of maternal behavior. In the present study, small bilateral electrolyte lesions in the MPOA of lactating females abolished nest building and retrieving components of maternal behavior while crouching and nursing were unaffected. Animals which failed to show retrieval and nest building behaviors tended to have a greater area of lesion within the more dorsal part of the MPOA. Although the dorsal MPOA may play a role in the maintenance of the active components of maternal behavior, i.e. nest building and retrieving, another critical factor in determining which components of maternal behavior are disrupted may be the size of the lesion. As one increases the area of damaged tissue there is also an accompanying increase in the components of maternal behavior which are disrupted. No correlation was found between damage to the Sexually Dimorphic Nucleus of the preoptic area and retrieving and nest building.

Animals↗

The Involvement of GABAA receptors in the control of GnRH and beta-endorphin release, and catecholaminergic activity in the preoptic area in anestrous ewes.

This study examined role of GABA A receptors in the control of GnRH, beta-endorphin release and catecholaminergic system activity in the preoptic area and LH secretion in anestrous ewes. Stimulation of GABA A receptors in the medial preoptic area (MPOA) by muscimol attenuated GnRH release and dopaminergic system activity and increased extracellular noradrenaline (NE) and MHPG concentration. Muscimol has no evident effect on the extracellular concentration of beta-endorphin-like immunoreactivity (B-END-LI) in the MPOA. The decrease of LH pulse frequency and concentration of this hormone in blood plasma suggests that GABA A receptor agonist applied in the MPOA suppresses GnRH release from the GnRH axon terminals in the ventromedial hypothalamus-nucleus infundibularis region (VEN/NI) into the hypophyseal vascular system. Blockade of GABA A receptors with bicuculline did not change GnRH release, catecholaminergic activity, B-END-LI concentration in the MPOA, and LH release. The presented data indicate that activation of GABA A receptors in the MPOA decreases extracellular concentration of GnRH in this structure and LH level in the blood plasma thus suggesting that GABA may act in the MPOA to inhibit GnRH release in the VEN/NI. These results suggest that suppression of GnRH/LH release during muscimol treatment may result from activation of GABA A receptors on the GnRH perikarya and/or through GABA A receptor mechanism on the dopaminergic and noradrenergic system in the MPOA. Lack of changes in B-END-LI concentration during stimulation or blocking GABA A receptors suggests, that beta-endorphinergic system in the MPOA does not participate in the GABA A receptors mechanism modulating GnRH release.

Anestrus↗

Opioid peptides inhibit noradrenergic transmission in the preoptic area to block LH secretion: evidence from neonatally androgenised rats.

A series of experiments are described which show (a) that the release of noradrenaline in the preoptic area of rats is regulated by a presynaptic opioid receptor and, (b) that changes in the opioid control of preoptic noradrenaline release are associated with the anovulatory condition found in adult female rats which have been exposed to androgen neonatally. The experiments support the hypothesis that opioid-noradrenergic interaction in the preoptic area is an important component in the neural mechanism regulating gonadotrophin secretion.

Action Potentials↗

Glutamic acid decarboxylase activity of the preoptic area and hypothalamus is influenced by the serotonergic system.

The effect of the serotonergic system on glutamic acid decarboxylase (GAD) activity of the preoptic area and the hypothalamus was studied in female rats on the day of proestrus. A circadian rhythm of GAD activity was observed with higher values in rats killed at 1130 h than in rats killed at 1500 h. In rats bearing lesions of the median raphe nucleus (MRn), a nucleus that sends 5-hydroxytryptamine nerve terminals to the areas under study decreased GAD activity. On the contrary, electrochemical stimulation of the MRn enhanced GAD activity in intact rats killed at 1500 h, but not in those killed at 1130 h, an effect that was prevented by the injection of the 5-hydroxytryptamine antagonist, methysergide. Furthermore, the injection of 5-hydroxytryptamine into the third ventricle, either in intact rats in the afternoon or in MRn-lesioned rats in the morning, also increased GAD activity. The results of the present study suggest that activation of the serotonergic system increases GAD activity in the preoptic area and hypothalamus.

Animals↗

Behavioral activation by stimulation of a GABAergic mechanism in the preoptic area of rat.

The locomotor activity and grooming of conscious freely moving rats were recorded during a 60-min unilateral perfusion of the preoptic area with neuroactive compounds using the microdialysis technique. The GABA agonist, muscimol (10, 20 and 100 microM) induced a dose-dependent increase in locomotor activity and grooming which was attenuated by co-perfusion with the GABA antagonist, bicuculline (10 microM), and was blocked by systemic injection of haloperidol, a preferential dopamine D2 receptor antagonist (0.25 mg/kg). Muscimol-induced hyperactivity was associated with a simultaneous increase of striatal extracellular dopamine. These data suggest that the preoptic area is functionally linked with the extrapyramidal dopaminergic system possibly via GABAergic system.

Animals↗