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Axon sparing lesions of the medial preoptic area block female sexual behavior.

The role of the medial preoptic area (mPOA) in regulating female musk shrew sexual behavior was assessed with excitatory neurotoxin, N-methyl-D-aspartate (NMDA) lesions. Ovariectomized, testosterone-implanted females that received lesions in the mPOA were statistically less likely to show complete sex behavior as compared to controls. These data suggest that the mPOA plays an activational role in testosterone-induced female sexual behavior.

Animals↗

Fos expression in the sleep-active cell group of the ventrolateral preoptic area in the diurnal murid rodent, Arvicanthis niloticus.

The ventrolateral preoptic area (VLPO) of the nocturnal laboratory rat receives direct input from the retina and is active during sleep; however, nothing is known about VLPO function in day-active (diurnal) species. In the first study, we used 24-h videotaping of Arvicanthis niloticus, a diurnal murid rodent, to estimate the distribution of sleep and wakefulness across a 12:12 light-dark cycle. Based on behavioral data, A. niloticus were perfused at a time when the animals are inactive (zeitgeber time (ZT) 20) or at a time when they are awake and active (ZT 23). The brains were processed for immunocytochemistry for Fos, an immediate early gene product used as an index of neural activity. Animals had more Fos-immunoreactive (Fos+) cells in the VLPO at ZT 20 than at ZT 23. The pattern of change in Fos expression seen in this area suggest that the VLPO serves the same function in A. niloticus as in rats. Eye injections of cholera toxin (beta subunit) were used to identify the retinal inputs to the VLPO of A. niloticus. In these animals, the VLPO had only very sparse retinal inputs compared to the rat. Together, these results raise the possibility that inputs from the suprachiasmatic nucleus (SCN) or the retina affect neuronal activity in the VLPO differently in rats and A. niloticus, thereby, contributing to differences in their sleep/wake patterns.

Animals↗

The main olfactory system mediates pheromone-induced fos expression in the extended amygdala and preoptic area of the male Syrian hamster.

Copulation in male hamsters is stimulated by exposure to vaginal secretions of conspecifics. These pheromones also stimulate fos expression in neural areas that regulate copulation including: the medial nucleus of the amygdala, the bed nucleus of the stria terminalis, and the preoptic area. The pheromones in vaginal secretions are detected by both the main and accessory olfactory systems. However, the accessory system plays the greater role in the regulation of mating behavior and has direct connections with the medial nucleus of the amygdala and bed nucleus of the stria terminalis. The goal of the present study was to determine which system mediates the effect of pheromones on the stimulation of more central areas by deafferenting these systems in experienced male hamsters before exposure to vaginal secretions. Destruction of the receptors in the main olfactory system with zinc sulfate eliminated the increase in fos immunoreactivity in the amygdala, bed nucleus of the stria terminalis and preoptic area following exposure to sexually stimulating pheromones. Deafferentation of the accessory olfactory system by removing the vomeronasal organ had no effect on pheromone-induced fos expression in these areas. We conclude that neurons expressing fos following exposure to vaginal secretions are stimulated via the main olfactory system and are not associated with the expression of copulatory behavior.

Amygdala↗

Induced ovulation in aged female rats by L-dopa implants into the medial preoptic area.

Direct placement of L-dopa into the medial preoptic area (MPOA) of aged pseudopregnant or constant vaginal estrous female rats resulted in a reinitiation of vaginal cycles and ovulation. Similar treatment with L-dopa in the dorsomedial septum or cortex was ineffective. Direct placement of leucine into any of the three brain regions did not have an effect on ovarian function. Intermittent treatment with L-dopa to MPOA was found to reinstate and maintain vaginal cycles in constant estrous females only when administered on the day of vaginal estrus of successive cycles. These findings support the hypothesis that age-dependent disturbances in ovarian function may be initiated by changes in neurotransmitter metabolism within the central nervous system.

Age Factors↗

Influence of maternal grooming, sex and age on Fos immunoreactivity in the preoptic area of neonatal rats: implications for sexual differentiation.

The medial preoptic area (mPOA) of the hypothalamus contains a sexually dimorphic nucleus (SDN-POA) that is 5-7 times larger in males than females and which contributes to the development and expression of male-specific sex behaviors in adulthood. Aside from a critical role for estrogen, the mechanisms that establish and maintain this sex difference are largely unknown. Differences in the size of the SDN-POA are thought to be related to estrogen-associated effects on programmed cell death (apoptosis) during early neonatal development. The expression of male sex behavior is also influenced by maternal behavior during development. During the postnatal period, the dam grooms the anogenital region of the pups to stimulate urination and defecation; however, male pups are groomed significantly more often than females and this maternal attention influences the expression of normal male sexual behavior in adulthood. Based on these observations, we hypothesized that different amounts of anogenital sensory stimulation might contribute to the sexually dimorphic development of the SDN-POA, specifically by providing for different levels of neuronal activation in the SDN-POA resulting in different degrees of cell death. Two experiments were conducted to test this hypothesis. In the first experiment, male and female rat pups on postnatal day 3 (PN 3) received simulated anogenital grooming with a stiff bristle paint brush. One hour later, the brains were removed and sections through the POA were cut and processed for the immunocytochemical detection of Fos-like immunoreactivity (IR) as an indicator of neuronal activation. In the second experiment, male and female littermates were killed on PN 3, 5, 7 and 12 and the number of Fos-immunoreactive cells and pyknotic cells detected in the SDN-POA were counted and compared. Our data demonstrate that anogenital stimulation on PN 3 results in a rapid induction of Fos-immunoreactive in the POA of both males and females. However, the majority of Fos-immunoreactive cells were located in the ventral POA and were distinctly lacking in the SDN-POA. In experiment 2, again no Fos-immunoreactive cells were detected in the SDN-POA of animals examined on PN 5-12. However, there was an increase in the number of pyknotic cells in the area surrounding and including the SDN-POA of females relative to males at PN 5, 7 and 12. Collectively, the data suggest that (1) anogenital grooming during early postnatal development induces a rapid activation of cells in the ventral mPOA, but not in the SDN-POA of rats, (2) there is a greater incidence of cell death in and around the SDN-POA of females vs. males during neonatal development, particularly toward the end of the hormone-sensitive critical period, and (3) Fos expression does not appear to be correlated with the sexually dimorphic development of, and/or programmed cell death within, the developing SDN-POA.

Aging↗

Role of the dorsomedial hypothalamus in thermogenesis and tachycardia caused by microinjection of prostaglandin E2 into the preoptic area in anesthetized rats.

Prostaglandin E2 (PGE2) acts in the preoptic area (POA) of the mammalian hypothalamus to increase body temperature and heart rate. Chemical stimulation of the dorsomedial hypothalamus (DMH), a region richly innervated by neurons in the POA, evokes sympathetically-mediated increases in heart rate and body temperature. We tested the hypothesis that neurons in the DMH mediate hyperthermia and tachycardia resulting from the action of PGE2 in the POA. Microinjection of PGE2 150 pmol/15 nl into the POA in urethane-anesthetized rats caused increases in body temperature and heart rate that were sharply reversed after injection of muscimol 80 pmol/100 nl into the DMH but not after similar injection of saline vehicle. Therefore, thermogenic and tachycardic actions of PGE2 in the POA are at least in part a consequence of neuronal activity in the region of the DMH.

Anesthetics, Intravenous↗

[Morphometric analysis of the vascular network in the preoptic area of the brain in man].

Twenty brains of human beings of both sex aged 17-64 were used for morphometric analysis of the vascular network of preoptic area. Blood vessels of the brain were filled by the mixture od India ink and gelatine. Serial resections 200 microns thick were illuminated by the method of Spalteholz. Standard stereologic parameters--volume density, surface density and the average half diameter of blood vessels were used for the quantification of capillary blood network density. By the comparative test of obtained mean values of males and females no statistically significant differences pertaining to sex and in respect to the size and density of capillary network in preoptic area were confirmed. This fact supported the assumption that although there were no morphologic differences in the blood network changes in various functional states, accompanying neuroendocrine events in the body of adults were in all probability the main and responsible factors inducing greater or less vascularization of specific organs.

Adolescent↗

The induction by testosterone of aromatase activity in the preoptic area and activation of copulatory behavior.

A series of 4 experiments was designed to study the relationships between the activity of the aromatase (AA) in the preoptic area (POA) and the activation by testosterone (T) of copulatory behavior in gonadectomized male and female Japanese quail. The induction of AA by T in the POA is dose- and time-dependent. Levels of AA seen in sexually mature males are restored in castrated birds by a treatment with 20 to 40 mm silastic T capsules which produce physiological levels of steroid in the plasma. The minimal dose of T (10 mm implant) which reliably restores copulatory behavior approximately doubles the AA in the POA. The induction of AA is significantly larger in males than in females. A significant increase in AA is observed within 16 hours after the start of the treatment with T and the induction is maximal after 48 hours. Activation of copulatory behavior follows a similar time course but occurs with a delay of 24-48 hours. These results thus suggest that, in male quail, the activity of the aromatase in the POA is a limiting factor in the activation of copulatory behavior. This idea is confirmed by direct experimentation using an aromatase inhibitor, androstatrienedione (ATD). If T-treated birds receive at the same time silastic implants filled with ATD, the activation of behavior is suppressed for at least one week. This behavioral inhibition is, as expected, accompanied and very probably caused by the inhibition of the aromatase activity in the preoptic area and anterior hypothalamus. No increase of enzyme activity over the level seen in castrates was actually detected during the first 8 days of exposure to T. A moderate increase in AA was seen on day 16 and is probably responsible for the behavioral activation which was observed at the end of the experiment.

Androstatrienes↗

Discrete electrolytic lesion of the preoptic area prevents LPS-induced behavioral fever in toads.

The preoptic area (POA) plays an important role in fever in mammals, but the role of this region in fever in ectothermic vertebrates has never been assessed. Toads, like all ectotherms, regulate their body temperature (T(b)) primarily by behavior and develop behavioral fever when injected with lipopolysaccharide (LPS). Therefore, we tested the hypothesis that the POA plays a role in the behavioral fever induced by LPS in the toad Bufo paracnemis. We made electrolytic lesions in the POA of toads (0.3 mA, 8 s) and measured preferred T(b) using a thermal gradient. After a period of 24h inside the gradient chamber, control, sham-operated and lesioned toads were systemically injected with LPS (200 micro g kg(-1)) or pyrogen-free saline. There was no significant effect of POA lesion in animals at their normal preferred T(b). LPS caused a significant increase in preferred T(b) of control and sham-operated toads, but lesions in the POA abolished this response. These results indicate that the POA is an important site in the central nervous system of toads, and perhaps of all vertebrates, involved in the development of fever.

Animals↗

Prenatal androgen exposure, preoptic area and reproductive functions in the female rat.

Pregnant rats were injected with 4 mg of testosterone propionate (TP) from days 15 to 22 of pregnancy or a single dose of 4 mg TP on day 17 or 21 of pregnancy. Female offspring treated with TP or the vehicle prenatally were sacrificed at 90 days of age. The volume of the cluster of intensely stained neurons in the medial preoptic area, the "sexually dimorphic nucleus of the preoptic area" (SDN-POA), was found to be affected by prenatal exposure to TP. The effect of TP on the development of the SDN-POA was most remarkable in the animals treated with a single dose of TP on day 17 of pregnancy, whereas TP injection on day 21 of pregnancy had no remarkable effect. These results suggest that continuous prenatal exposure to TP is not essential for stimulation of the development of the SDN-POA, suggesting the presence of a critical period during which the SDN-POA is most sensitive to the androgen. Although 4 out of 11 females exposed to TP from days 15 to 22 were sterile, the ovarian function of most of the TP-exposed offspring was normal. Furthermore, prenatally TP-exposed females failed to show behavioral masculinization and defeminization. All these females displayed high lordotic response levels and only rarely showed mounting behavior. These results suggest that the absolute volume of the SDN-POA does not seem to be directly correlated with the regulation of the cyclic release of gonadotropins and/or expression of sexual behavior.

Animals↗

Prenatal ethanol and the prepubertal sexually dimorphic nucleus of the preoptic area.

The volume of the sexually dimorphic nucleus of the preoptic area of the hypothalamus (SDN-POA) was determined in 14-31-day-old male and female rats whose mothers received a liquid diet containing 5% w/v ethanol from day 8 of gestation to parturition. Pair-fed dams received as a nutritional control an equal volume of an isocaloric liquid diet with maltose-dextrin in place of ethanol. Normal controls had laboratory rat chow and water available ad lib. The SDN-POA volume of ethanol-exposed males was significantly reduced compared to the pair-fed and normal males, and became indistinguishable from the SDN-POA volumes of the pair-fed and normal females. Ethanol-treated females also had a markedly reduced SDN-POA volume compared to the pair-fed and normal females. Our findings indicate that the SDN-POA of prepubertal rats of both sexes is sensitive to the effects of in utero ethanol exposure. While plasma testosterone, progesterone and estradiol titers, which we measured in fetuses on gestation day 22, were differentially affected by maternal ethanol consumption, the alterations by themselves cannot adequately explain the effects of prenatal ethanol exposure on the developing SDN-POA.

Animals↗

The nitric oxide-guanosine 3',5'-cyclic monophosphate pathway regulates dopamine efflux in the medial preoptic area and copulation in male rats.

Dopamine in the medial preoptic area (MPOA) plays a significant role in regulation of male copulation. One mediator of the MPOA dopamine level is nitric oxide. In the current study, we investigated the role of the nitric oxide-guanosine 3',5'-cyclic monophosphate (cGMP) pathway in the regulation of MPOA dopamine and copulation in male rats. The reverse-dialysis of a membrane-permeable analog, 8-Br-cGMP, increased, while a soluble guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ), significantly reduced basal dopamine and its metabolite levels. ODQ successfully blocked a nitric oxide donor-induced increase in dopamine levels, while a neuronal nitric oxide synthase (nNOS) inhibitor was ineffective in blocking an 8-Br-cGMP-induced increase in dopamine, indicating that cGMP is "downstream" of nitric oxide. Furthermore, 8-Br-cGMP facilitated, while ODQ inhibited copulation. Given the steroid-sensitive nature of nNOS functions and the multiple roles nitric oxide plays in the MPOA, we propose that nitric oxide provides important integration of various neurochemical and neuroendocrine signals. The involvement of the central nitric oxide-cGMP pathway in the regulation of copulation also raises an interesting therapeutic possibility, as the manipulation of the same pathway in peripheral tissue is already utilized in treatment of male sexual dysfunction.

3,4-Dihydroxyphenylacetic Acid↗

Analysis of brainstem A1 and A2 noradrenergic inputs to the preoptic area using microdialysis in the rat.

Noradrenergic inputs to the preoptic area (POA) are involved in regulating a variety of homeostatic functions. However, the accurate measurement of endogenous noradrenaline (NA) release in the POA has been difficult to achieve and consequently little has been done to characterise the different noradrenergic pathways. By combining the technique of intracranial microdialysis with tissue pre-loading of [3H]NA we have developed a sensitive index of NA release in the POA [8]. Using this method we have now examined and compared the effects of electrical stimulation of the brainstem A1 and A2 cell groups on NA release in the POA. Anaesthetised proestrus rats were implanted with microdialysis probes either unilaterally or bilaterally in the POA and stimulating electrodes positioned in either the A1 or A2 regions. Electrical stimulation (10 Hz, 10s on/off for 20 min) of the A1 region resulted in repeatable, calcium-dependent increases in radioactivity outflow from the ipsilateral POA (P < 0.01). A1-evoked release was twice as large as that observed after equivalent 10 Hz electrical stimulation of the A2 region (P < 0.05). In experiments using bilateral POA microdialysis and A1 stimulation, a significant increase in release from the contralateral POA, amounting to approximately 80% of that observed in the ipsilateral POA, was observed. Experiments involving the blockade of A1-stimulated release in the ipsilateral POA by perfusion with a calcium-free medium demonstrated that increases in radioactivity measured in the contralateral POA were not originating from the ipsilateral POA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Comparison of the expression of two immediate early gene proteins, FosB and Fos in the rat preoptic area, hypothalamus and brainstem during pregnancy, parturition and lactation.

Medial preoptic area (MPA), supraoptic nucleus (SON), magnocellular (MaPVN) and parvocellular (PaPVN) paraventricular hypothalamic nuclei, and mesencephalic lateral tegmentum (MLT) are involved in maternal behavior, parturition and lactation. This study investigated the FosB and Fos immunoreactivity in these regions of virgin, pregnant, parturient, lactating, and lactating-arrested rats. The patterns of FosB and Fos expression were compared between the sections taken from the same animals. Quantitative immunohistochemistry revealed a significant increase in the numbers of FosB-positive neurons in the MPA, SON, MaPVN, and MLT of parturient and lactating females as compared with pregnant or virgin animals. In lactating rats, the numbers of FosB-positive neurons in the MPA, PaPVN, and MLT were increased, but the numbers in the SON and MaPVN were decreased as compared with parturient females. Many Fos-positive neurons were also seen in parturient and lactating rats, and the patterns of Fos expression in each region were quite similar to those of FosB. Moreover, double-labeling immunohistochemistry revealed that: (1) many FosB-positive nuclei were observed in oxytocin and vasopressin neurons of the SON and PVN in parturient rats; (2) within FosB-positive neurons, 89.5% in the MPA, 86.8% in the MLT of parturient rats, and 92% in the MPA and 90.8% in the MLT of lactating animals were also Fos-positive. Only a small number of FosB and Fos-positive neurons were seen in females that were killed in the early stage of parturition. Removal of the litters immediately after parturition completely eliminated FosB and Fos expression in each region in the dams. Taken together, the present results suggest that FosB expression is co-involved with Fos in the neural activation during parturition and lactation in rats.

Animals↗

Release rates of catecholamines, GABA and beta-endorphin in the preoptic area and the mediobasal hypothalamus of the rhesus monkey in push-pull perfusates: correlation with blood hormone levels.

Push-pull cannulae were implanted into the preoptic area and into the mediobasal hypothalamic median eminence complex of ovariectomized rhesus monkeys. After recovery, perfusion of the implanted areas was performed over a period of 56 h before and following estradiol benzoate treatment. This treatment results in a drop of LH levels followed by an increase. Catecholamine (norepinephrine, epinephrine and dopamine) concentrations in perfusates collected at 15 min intervals fluctuated tremendously prior to treatment with the estrogen. These fluctuations were largely reduced in perfusates of both structures following the estrogen treatment. They reoccurred at the time of increasing LH levels. beta-endorphin and GABA concentrations were also measured in the perfusates of both structures. Occasional secretory bursts were observed without any obvious relation to the estrogen treatment. It is concluded that catecholamine release in the preoptic area and in the mediobasal hypothalamic median eminence complex is of a pulsatile nature in ovariectomized rhesus monkeys. This pulsatility is largely reduced or abolished following estrogen treatment. The reduced pulsatility may bear a signal character for the release of LH.

Animals↗

A diurnal fluctuation in medial basal hypothalamic-preoptic area cytosol estrogen receptors in ovariectomized hamsters.

Cytosol estrogen receptors (CER) were measured in ovariectomized hamsters, kept in a light:dark schedule of 14:10. Significant diurnal fluctuations in CER occurred in medial basal hypothalamus-preoptic area, but not in amygdala, anterior pituitary or uterus. Highest levels of CER in medial basal hypothalamus-preoptic area occurred 2 h before lights went out, and lowest levels 1 h after lights went out.

Animals↗

Thermoregulatory behaviour after repetitive cooling of the preoptic area and of the spinal cord in the rat.

The thermoregulatory behaviour of 6 rats was studied during exposure to cold and warm ambient temperatures after either the preoptic area or the cervical spinal cord had been intermittently cooled for an average of 130 h. The precooled animals worked more for heat in cold environments and for cool air in a warm environment than the control animals. This behaviour, probably due to a decreased ability of the precooled animals to retain heat, suggested that the precooled animals were not fully adapted to cold. 1974) will learn to press a lever to modify their thermal environment, and this paper describes the thermoregulatory behaviour of rats after prolonged cooling of the preoptic area, and of the spinal cord. The thermoregulatory behaviour of cold exposed and cold adapted animals has already been studied in several species (Carlton and Marks, 1958; Laties and Weiss, 1960; Revusky, 1966; balwin and Ingram, 1967).

Adaptation, Physiological↗

Mediation of norepinephrine-stimulated cyclic AMP accumulation by adrenergic receptors in hypothalamic and preoptic area slices: effects of estradiol.

Adrenergic receptor agonists and antagonists were employed to establish (a) which receptor subtypes mediate the cyclic AMP response to norepinephrine in hypothalamic and preoptic area slices from gonadectomized female rats and (b) which receptor subtypes might be modulated by the steroid hormone estradiol. Slice cyclic AMP levels were elevated by the beta receptor agonist isoproterenol, but not by alpha 1 (phenylephrine, methoxamine) or alpha 2 (clonidine) agonists. However, the alpha agonist phenylephrine potentiated the effect of the beta agonist isoproterenol on slice cyclic AMP accumulation. In slices from rats given no hormone treatment, the beta antagonist propranolol inhibited norepinephrine-stimulated cyclic AMP production, while the alpha 1 antagonist prazosin was without effect. In contrast, the cyclic AMP response to norepinephrine in slices from estradiol-treated rats was blocked more effectively by prazosin than by propranolol. Estradiol treatment also attenuated the production of cyclic AMP by the beta agonist isoproterenol. The data suggest (a) that norepinephrine induction of cyclic AMP accumulation in hypothalamic and preoptic area slices is mediated by beta receptors and potentiated by alpha receptor activation and (b) that estradiol depresses beta and increases alpha 1 receptor function in slices from brain regions associated with reproductive physiology.

1-Methyl-3-isobutylxanthine↗