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PubMed2000

Tyrosine kinase effects on adrenoceptor-stimulated cyclic AMP accumulation in preoptic area and hypothalamus of female rats: modulation by estradiol.

These studies examined the functional interactions between adrenergic G-protein coupled receptors and protein tyrosine kinases in the preoptic area and hypothalamus, brain regions that regulate reproductive function in female rats, and evaluated whether in vivo treatment with estradiol for 2 days modulates the cross-talk between these two signaling pathways. In hypothalamic slices genistein, a general tyrosine kinase inhibitor, enhances norepinephrine-stimulated cAMP synthesis independent of estradiol treatment. Genistein appears to act by increasing beta-adrenoceptor signaling. At high norepinephrine concentrations, estradiol potentiates genistein enhancement of the cAMP response in hypothalamic slices. This interaction between estradiol and genistein appears to involve modification of alpha(2)-adrenoceptor signaling mechanisms. In preoptic area slices, genistein enhancement of norepinephrine-stimulated cAMP synthesis is only observed in estradiol-treated rats. In this brain region, genistein enhances cAMP accumulation by modifying alpha(1)- and/or alpha(2)-adrenoceptor rather than beta-adrenoceptor signaling. Genistein amplification of norepinephrine-stimulated cAMP synthesis is not mediated by interactions with estrogen receptors, or by regulation of adenylyl cyclase or phosphodiesterase activities. At the concentration used, genistein inhibits tyrosine phosphorylation in slices from both brain regions. Daidzein, an inactive analogue of genistein, fails to enhance the norepinephrine-stimulated cAMP response in either brain region independent of hormone treatment. These results suggest that protein tyrosine kinases regulate adrenergic responses in the hypothalamus and preoptic area. Moreover, the functional interaction between adrenergic G-protein coupled receptor signaling and protein tyrosine kinases is modified in a brain region and receptor subtype specific manner by estradiol.

Adrenergic alpha-Agonists↗
PubMed2003

GABA and glutamate in mating-activated cells in the preoptic area and medial amygdala of male gerbils.

The posterodorsal medial amygdala (MeApd), the posterodorsal preoptic nucleus (PdPN), and the medial cell group of the sexually dimorphic preoptic area (mSDA) contain cells that are activated specifically at ejaculation as assessed by Fos expression. The mSDA also expresses Fos early in the mating context. Because little is known about the neurotransmitters of these activated cells, the possibility that they use gamma-aminobutyric acid (GABA) or glutamate was assessed. Putative glutamatergic cells were visualized with immunocytochemistry (ICC) for glutamate and its neuron-specific transporter. Their distributions were compared with those of GABAergic cells visualized with ICC for the 67-kDa form of glutamic acid decarboxylase (GAD(67)) and in situ hybridization for GAD(67) messenger RNA (mRNA). Colocalization of Fos and GAD(67) mRNA in recently mated males indicated that half of the activated cells in the PdPN, mSDA, and lateral MeApd are GABAergic. Colocalization of Fos and glutamate suggested that a quarter of the activated mSDA and lateral MeApd cells are glutamatergic. The PdPN does not appear to have glutamatergic cells. In the lateral MeApd, the percentage of activated cells that are GABAergic (45%) matches the percentage that project to the principal part of the bed nucleus of the stria terminalis (BST; 43%), and the percentage likely to be glutamatergic (27%) matches the percentage projecting to the mSDA (27%). The latter could help to trigger ejaculation. The distribution of GABAergic and putative glutamatergic cells in the caudal preoptic area, caudal BST, and medial amygdala of male gerbils is also described.

Amygdala↗
PubMed1992

Acoustic modulation of neural activity in the preoptic area and ventral hypothalamus of the green treefrog (Hyla cinerea).

Responses of neurons in the preoptic area and ventral hypothalamus to conspecific mating calls or white noise bursts were examined in male green treefrogs (Hyla cinerea) during different seasons. In the winter, 34.3% of preoptic neurons and 46.7% of ventral hypothalamic cells demonstrated significant changes in activity level during presentation of a conspecific mating call. In contrast, only 13.3% of preoptic units and 16.7% of ventral hypothalamic cells responded to the white noise. The percentage of preoptic and hypothalamic units responding to the advertisement call did not differ significantly during the summer breeding season. Type I units exhibited a dramatic increase in activity during acoustic stimulation followed by a rapid return to baseline activity levels after stimulus offset. Type II cells showed a robust activity increase during stimulation, but maintained an intermediate activity level after stimulus offset. In the preoptic area, a third response type exhibited suppressed activity during acoustic stimulation. Although seasonal condition did not alter the percentage of acoustically responsive units within either nucleus, the proportion of Type I units in the ventral hypothalamus was greatest during the summer.

Acoustic Stimulation↗
PubMed1993

Distribution of estrogen receptor-immunoreactive cells in the preoptic area of the ewe: co-localization with glutamic acid decarboxylase but not luteinizing hormone-releasing hormone.

Using immunocytochemical techniques we have examined the distribution of cells containing estrogen receptors (ERs) in the preoptic and anterior hypothalamic regions of short-term (1 week) ovariectomized ewes. Subsequent double-labelling experiments examined the co-localization patterns of ER and luteinizing hormone-releasing hormone (LHRH) or glutamic acid decarboxylase (GAD) immunoreactivities. ER-immunoreactive (-IR) cells were identified throughout the central and medial aspects of the preoptic area in a continuum which begins at the level of the organum vasculosum of the lamina terminalis and terminates in the caudal anterior hypothalamic area. A conspicuous sub-population of densely clustered ER-IR cells was identified within this distribution extending from the central region of the preoptic area into the bed nucleus of the stria terminalis. ER-IR cells were also identified in the ventrolateral septum and supraoptic nuclei. Double-labelling experiments showed that although rostral LHRH neurons were surrounded by ER-IR cells, they did not themselves possess ER immunoreactivity. In marked contrast, we estimate that approximately 40% of GAD-IR cells in the central aspect of the medial preoptic area are immunoreactive for the ER and that these cells account for nearly 30% of all ER-IR cells in this region. These results indicate that, in common with other species, LHRH neurons in the ewe do not possess ERs and suggest therefore, that these neurons are unlikely to be modulated directly by circulating estrogens. However, large numbers of adjacent GABA neurons possess ERs and may comprise a major neuronal population mediating gonadal steroid input to LHRH neurons.

Animals↗
PubMed2001

Preoptic area sleep-regulating mechanisms.

Evidence is summarized for the existence of a sleep-regulating mechanism within the preoptic area of the hypothalamus, including the results of lesion, stimulation, and neuronal recording studies. Recent findings employing the c-fos protein immunohistochemical method, have localized putative sleep-regulatory neurons to the ventrolateral preoptic area (vlPOA) and the median preoptic nucleus (MnPn). Electrophysiological studies have confirmed the presence of neurons with sleep-related discharge in the vlPOA. Neurons in the vlPOA that exhibit c-fos protein immunoreactivity during sleep contain the inhibitory neuromodulators galanin and gamma-aminobutyric acid (GABA). These neurons also project to monoaminergic arousal systems, particularly the histaminergic cell groups in the posterior hypothalamus. POA neurons can be hypothesized to provide sleep-related inhibitory control over multiple arousal systems in the forebrain and brainstem.

Action Potentials↗
PubMed2004

Medial preoptic area delta-opioid receptors inhibit lordosis.

Endogenous opioid peptides that activate the delta-opioid receptor (DOR) are thought to facilitate female receptive behavior. This facilitation of lordosis has been demonstrated by intracerebroventricular infusions and injection of DOR-active ligands into the ventromedial hypothalamic nucleus, an area with robust DOR binding. However, DOR binding is distributed throughout the hypothalamus, and the role of DOR in other areas of the hypothalamus has not been examined. In the current study, we demonstrated DOR immunoreactivity in the medial preoptic area (MPO), in particular medial preoptic nucleus (MPN) of the preoptic area. DOR immunoreactive processes were sparsely distributed in the medial and lateral parts of the MPN. Larger DOR immunoreactive fibers were localized in the ventrolateral aspect of the lateral MPN. The MPN is involved in the modulation of female sexual receptivity and the distribution of DOR in this area suggested to us that DOR may regulate lordosis. Ovariectomized rats with unilateral cannulae aimed at the MPN were given 5microg 17beta-estradiol benzoate (EB), once every 4 days and tested for lordosis. [D-Pen(2), D-Pen(5)]-enkephalin (DPDPE), a DOR agonist, microinfused into the MPO, 52-54h after EB-priming, inhibited lordosis when compared with the aCSF (vehicle) control (P <== 0.05). The inhibitory effects of DPDPE were reversed by microinjection of naltrindole, a DOR antagonist (P <== 0.05). Interestingly, the DOR inhibition of lordosis is similar to the micro-opioid receptor inhibition of lordosis in the MPN. These results indicate that DOR in the MPO, particularly in the MPNm, plays an important role in the regulation of lordosis.

Animals↗
PubMed1981

Water intake elicited by injections of angiotensin II into preoptic area of rats.

Drinking in response to unilateral injections of angiotensin II (AII) into the preoptic area is relatively weak and a relatively high dose of AII is required. A comparison was made of the drinking elicited by bilateral and unilateral injections of AII. Reliable drinking was observed when 5 X 10(-12) mol of AII in 0.2 microliter was injected bilaterally into the preoptic area, and in some animals when the dose of AII was 0.5 X 10(-12) mol in 0.2 microliter. The volumes of water intake were significantly larger with bilateral injections compared to unilateral injections. By injection of tritiated AII to elicit drinking and subsequent autoradiographic analysis of brain sections, it was shown that the injections were confined to the preoptic region and did not reach the cerebral ventricles. The results suggest that 1) bilateral injections may be more appropriate for comparing the preoptic region with other putative angiotensin receptive sites, 2) there is a greater responsiveness of the preoptic region to bilateral as compared with unilateral injections, and 3) the AII receptive area is diffusely represented in the region of the medial preoptic nucleus.

Angiotensin II↗
PubMed1988

Quantitative analysis of synaptic input to gonadotropin-releasing hormone neurons in normal mice and hpg mice with preoptic area grafts.

Mutant hypogonadal (hpg) mice with a truncated gene for the precursor to gonadotropin-releasing hormone (GnRH) show certain aspects of recovery of reproductive function after receiving grafts of normal preoptic area into the third ventricle. We have previously shown that GnRH neurons from within the grafts can innervate the appropriate neural-hemal target in the host. To determine if in turn these exogenously derived neurons receive a synaptic input comparable to the GnRH neurons in the normal animal we have now carried out a quantitative ultrastructural analysis to compare the synaptic input to GnRH neurons in the normal preoptic area and in the grafts. In almost all cases GnRH cells or dendrites in normal brains and within the grafts received a synaptic input. In normal animals, input to GnRH dendritic profiles was significantly greater (P less than 0.001) than to the somatic plasma membrane and this trend was also observed within the grafts though the difference was not statistically significant. In addition, no statistically significant difference was found between the input to GnRH structures within the grafts and in normal preoptic area. However, a substantial variability in input among grafted animals was evident which was not observed in normal animals. The sources of variability within the grafts are discussed and we suggest that the deficiencies and differences that exist in regulation of gonadotropin secretion among grafted hpg animals may be reflected in aberrant synaptic input.

Animals↗
PubMed1991

Prodynorphin- and substance P-containing neurons project to the medial preoptic area in the male Syrian hamster brain.

To determine if substance P- or prodynorphin-containing neurons of the medial nucleus of the amygdala and medial bed nucleus of the stria terminalis send projections to the medial preoptic area in the male Syrian hamster, we placed a fluorescent retrograde tract tracer (either Fluoro-gold, or rhodamine- or fluorescein-impregnated latex microspheres) into the medial preoptic area. Five to seven days later, the animals were treated with colchicine, allowed to survive for 48 h and the brains were processed for immunofluorescence histochemistry. Tissue sections were incubated in either rat anti-substance P or rabbit anti-C-peptide (the C-terminal sequence of dynorphin B) antiserum followed by incubation in either fluorescein- or rhodamine-conjugated anti-rabbit or anti-rat antiserum. When the injection site of retrograde tracer was centered within the caudal one-third of the medial preoptic area, labeled cell bodies were observed caudally in the medial part of the bed nucleus of the stria terminalis. Retrogradely labeled cell bodies were also observed in the posterodorsal subdivision of the medial nucleus of the amygdala. Both prodynorphin and substance P immunolabeling were observed in retrogradely labeled neurons in these two areas but fewer of these projection neurons were immunolabeled with substance P antiserum than with C-peptide antiserum. These projections may play a role in the peptidergic modulation of reproductive behavior in this species.

Amygdala↗
PubMed1990

Diazepam inhibits stimulating effect of cooling preoptic area on antibody production.

To clarify the mechanism of the stimulating effect of fever on the primary antibody response, rats were immunized with sheep erythrocytes, and a fever-like response was induced by cooling the preoptic area for five days. Diazepam, 0.5 mg/kg, given daily during the cooling time, did not affect the normal antibody response of the control animals nor did it prevent the rise in body temperature elicited by cooling the preoptic area but it did, nevertheless, strongly reduce the stimulating effect of this procedure on antibody production. A smaller reduction of this effect was also seen in adrenalectomized rats in which a physiological and stable plasma level of corticosterone was maintained. Because diazepam suppresses some sympathetic and endocrine responses to stress, these data suggest that the effect of cooling the preoptic area on the primary antibody response, and, by inference, that of fever, is to a large extent mediated by the adrenal and other stress response or responses to the cold stimulus. The results do not, however, exclude the possibility of an additional, direct effect of the elevated body temperature on immunocompetent cells.

Adrenalectomy↗
PubMed1992

Characterization of the hypnotic effects of triazolam microinjections into the medial preoptic area.

We have previously reported that microinjections of the benzodiazepine hypnotic triazolam into the medial preoptic area (MPA) of the hypothalamus enhance sleep in rats. The present study further characterizes this effect, by examining its anatomical specificity, determining whether it is mediated by interaction with central benzodiazepine receptors, and assessing whether sleep induction is associated with changes in core temperature. It was found that microinjections of 0.25 and 0.5 micrograms triazolam into two nearby structures, the lateral preoptic area and diagonal band of Broca, failed to alter sleep. Total sleep time was enhanced by microinjection of triazolam into the MPA, and this effect was blocked by co-administration of the benzodiazepine receptor blocker RO 15-1788. Sleep enhancement by triazolam was not associated with significant alterations in core body temperature. These observations continue to suggest that the MPA may be a site which mediates the hypnotic effect of triazolam, and add to the growing body of data emphasizing the importance of hypothalamic function in the regulation of sleep and waking.

Body Temperature↗
PubMed1992

A cyclic AMP mechanism mediates the serotonin-induced increase in glutamic acid decarboxylase activity in the preoptic area and hypothalamus.

Previous studies have shown that the injection of 5-hydroxytryptamine (5-HT) into the third ventricle of rats on the afternoon of proestrus increases glutamic acid decarboxylase (GAD) activity in the preoptic area and the hypothalamus. In the present report we examine the adenylate cyclase-cyclic AMP (cAMP) system as mediator of that effect. The increase in GAD activity induced by intraventricular injection of 5-HT was completely blocked by injecting an antiserum against cAMP into the third ventricle 30 min earlier, whereas an injection of serum from normal rabbits was ineffective. On the contrary, activation of adenylate cyclase activity by intraventricular injection of forskolin increased GAD activity, an effect that was also blocked by anti-cAMP serum. Anti-cAMP serum also lowered GAD activity in the preoptic area and hypothalamus when injected on the morning of proestrus but not when injected in the afternoon, when the values of GAD activity were already low. The results suggest that a cAMP mechanism may be involved in the changes in preoptic-area and hypothalamic GAD activity such as the rise in enzyme activity induced by intraventricular injection of 5-HT.

Animals↗
PubMed1992

The involvement of the hypothalamic preoptic area on the regulation of thirst in the rat.

Acute reversible lesion in the medial preoptic area (MPOA) by unilateral injection of the local anesthetic lidocaine chlorhydrate (1 microliter, 20 ng/microliters) causes a transient increase in water intake induced by water deprivation in rats. Since lidocaine suppresses the nervous activity, leaving intact fibers of passage and blood vessels, the results suggest an intrinsic inhibitory action of the MPOA on the regulation of water intake. Drinking elicited a return to volumes similar to those of control rats, 3-4 h after lidocaine administration. Lidocaine released into the lateral preoptic area (LPO) slightly decreased or did not change water intake, as compared with controls. The urinary excretion in the MPO group was higher than that of the controls and the LPO, while this last group excreted significantly less urine. The ablation of the POA with lidocaine suggests that the medial aspect of the POA has an intrinsic inhibitory factor influencing drinking, while the lateral aspect did not show a relevant effect.

Animals↗
PubMed1985

Formation of the sexually dimorphic nucleus of the preoptic area: neuronal growth, migration and changes in cell number.

The sexually dimorphic nucleus of the preoptic area (SDN-POA) appears to be a morphological marker of the process of sexual differentiation of the rat brain. A portion of the presumptive SDN-POA neurons can be specifically identified utilizing autoradiography following the administration of [3H]thymidine on day 18 of gestation. In the present study we have utilized this fact in order to describe the general pattern of formation of the SDN-POA during the perinatal period. Following the administration of [3H]thymidine, fetal pups were sacrificed and perfused with neutral formalin either two hours after the injection or on day 20 or 22 postfertilization. Neonatal pups were either sacrificed and perfused or assigned to one of the treatment groups. Male pups were either gonadectomized or sham gonadectomized; females were all sham gonadectomized. These pups were then sacrificed and perfused on either day 26, 28 or 32 postfertilization. All brains were processed for autoradiography. The size, number and location of labeled cells within the medial preoptic area (MPOA) was determined. In general it appears that the labeled cells grow in size during the early postnatal period. These cells also migrate from the more ventral aspects of the MPOA to aggregate and form the SDN-POA. Furthermore, there is a significant decrease in the number of labeled cells by day 32 postfertilization (day 10 of postnatal life) which appears to contribute to the specific labeling of the SDN-POA of the adult animal. However, results obtained in this study from quantitative analyses do not indicate that sex or the postnatal steroid hormone environment influence the processes of growth, migration and decrease in MPOA cell number of those presumptive SDN-POA cells born specifically on day 18 of gestation and analyzed in this study.

Animals↗
PubMed1976

Immunoreactive luteinizing hormone releasing factor in pituitary stalk blood from female rats: sex steroid modulation of response to electrical stimulation of preoptic area or median eminence.

The effects of sex steroid hormones on the responsiveness of the neural mechanism responsible for the secretion of LH-RF have been examined in the female rat. Responsiveness was determined at pro-oestrus by measuring the increments in immunoreactive LH-RF of pituitary stalk blood produced by electrical stimulation of the medial preoptic area or median eminence. Ovariectomy on the morning of dioestrus reduced the LH-RF response to preoptic stimulation while oestradiol benzoate (OB) or testosterone propionate (TP) administered immediately after ovariectomy significantly augmented the response. The facilitatory effect of TP was possibly due to its conversion to an aromatized derivative since 5alpha-dihydrotestosterone monobenzoate was ineffective. Progesterone did not facilitate preoptic responsiveness, and, when administered to animals ovariectomized at 12.00 h of pro-oestrus, reduced the LH-RF response at 18.00 h the same day. Stimulation of the median eminence produced a significantly greater increment in LH-RF than stimulation of the preoptic area. The facilitatory action of OB on the LH-RF response was less marked for median eminence compared with preoptic stimulation. The administration of ICI 46474 at 17.00 h of dioestrus did not reduce preoptic responsiveness on the morning of the next day, suggesting that this compound does not act as an 'antioestrogen' at the level of the preoptic area.

Animals↗
PubMed2000

The distribution of cells containing estrogen receptor-alpha (ERalpha) and ERbeta messenger ribonucleic acid in the preoptic area and hypothalamus of the sheep: comparison of males and females.

We have used in situ hybridization to compare the distributions of estrogen receptor alpha (ERalpha) and ERbeta messenger RNA (mRNA)-containing cells in the preoptic area and hypothalamus of ewes and rams. Perfusion-fixed brain tissue was collected from luteal phase ewes and intact rams (n = 4) during the breeding season. Matched pairs of sections were hybridized with sheep-specific, 35S-labeled riboprobes, and semiquantitative image analysis was performed on emulsion-dipped slides. A number of sex differences were observed, with females having a greater density of labeled cells than males (P < 0.001) and a greater number of silver grains per cell (P < 0.01) in the ventromedial nucleus for both ER subtypes. In addition, in the retrochiasmatic area, males had a greater (P < 0.05) cell density for ERalpha mRNA-containing cells than females, whereas in the paraventricular nucleus, females had a greater density (P < 0.05) of ERalpha mRNA-containing cells than males. There was a trend (P = 0.068) in the arcuate nucleus for males to have a greater number of silver grains per cell labeled for ERalpha mRNA. In both sexes, there was considerable overlap in the distributions of ERalpha and ERbeta mRNA-containing cells, but the density of labeled cells within each nucleus differed in a number of instances. Nuclei that contained a higher (P < 0.001) density of ERalpha than ERbeta mRNA-containing cells included the preoptic area, bed nucleus of the stria terminalis, and ventromedial nucleus, whereas the subfornical organ (P < 0.001), paraventricular nucleus (males only, P < 0.05), and retrochiasmatic nucleus (females only, P < 0.05) had a greater density of ERalpha than ERbeta mRNA-containing cells. The anterior hypothalamic area and supraoptic nucleus had similar densities of cells containing both ER subtypes. The lateral septum and arcuate nucleus contained only ERalpha, whereas only ERbeta mRNA-containing cells were seen in the zona incerta. The sex differences in the populations of ER mRNA-containing cells in the ventromedial and arcuate nuclei may explain in part the sex differences in the neuroendocrine and behavioral responses to localized estrogen treatment in these nuclei. Within sexes, the differences between the distributions of ERalpha and ERbeta mRNA-containing cells may reflect differential regulation of the actions of estrogen in the sheep hypothalamus. Low levels of ERbeta mRNA in the preoptic area and ventromedial and arcuate nuclei, regions known to be important for the regulation of reproduction, suggest that ERbeta may not be involved in these functions.

Animals↗
PubMedDate not supplied

[The direct activating influence of the lateral hypothalamic preoptic area on the thalamic synchronizing system].

In order to reveal the mechanisms of participation of the preoptic hypothalamic area in sleep-wake cycle regulation the effects of its electrical stimulation on activity of the thalamic median center were studied in chronic experiments in cats. Ipsi- and contralateral projections from the lateral preoptic area to the thalamic median center were electrophysiologically demonstrated. Activatory influence of the preoptic area was shown on the thalamic mechanisms of spindle activity generation. The obtained data suggest the interaction of the preoptic area with the structures of non-specific thalamus via the direct pathways to be one of the mechanisms of the preoptic area participation in sleep initiation and formation of the slow-wave sleep.

Animals↗
PubMed1995

Effects of prolonged social isolation on responses of neurons in the bed nucleus of the stria terminalis, preoptic area, and hypothalamic paraventricular nucleus to stimulation of the medial amygdala.

The studies presented demonstrate changes in hypothalamo-pituitary-adrenocortical secretion, and in electrical activity and synaptic responses of neurons in the bed nucleus of the stria terminalis, preoptic area, and hypothalamic paraventricular nucleus of rats exposed to early, long-term social isolation. Rats isolated from all social contact from an early preweaning time showed reduced basal plasma corticosterone concentrations, compared with littermate controls raised under social conditions. Isolated animals also exhibited a selective decrease in the spontaneous electrical activity of neurons within the hypothalamic paraventricular nucleus and lateral preoptic area, but not in adjacent structures. Moreover, isolation also altered the response of neurons in certain nuclei to electrical stimulation of the medial amygdala. Thus, a reduction in excitatory responses, and an increase in inhibition and nonresponsiveness, of preoptic area and paraventricular nucleus neurons was recorded, compared with control rats. Neurons in the bed nucleus of the stria terminalis were less affected, but showed an increase in the duration of excitatory responses following medial amygdala stimulation. These results, obtained from urethane-anesthetized rats, together with the reduced basal plasma corticosterone concentrations, suggest a reduction in limbic-hypothalamo-pituitary-adrenocortical (LHPA) activity following maternal deprivation and prolonged social isolation. This may result from altered limbic activity, specifically in the amygdala and its pathways to the paraventricular nucleus (PVN). Such alterations may include the stria terminalis, in so much as increased efficacy of inhibitory components and reduced efficacy of excitatory components was observed. The neural mechanisms underlying these alterations could involve an altered synaptology of the regions examined and/or a disruption of glucocorticoid feedback events.

Amygdala↗