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PubMed1997

Locus coeruleus lesions decrease norepinephrine input into the medial preoptic area and medial basal hypothalamus and block the LH, FSH and prolactin preovulatory surge.

The aim of this work was to study the role of the dorsal noradrenergic ascending pathway (DNAP), which originates in the locus coeruleus (LC) on the preovulatory surge of luteinizing hormone (LH) follicle-stimulating hormone (FSH) and prolactin (PRL) by producing bilateral electrolytic lesions (cathodal or anodal) in this nucleus. LC lesions were placed at 11.00 h on proestrus in female rats with regular 4-day estrous cycles. Intact rats, sham-operated as well as animals with missed lesions served as controls. In Experiment I, anodal current was applied and hourly blood samples were withdrawn (from 13.00 to 17.00 h) via a jugular catheter from conscious, freely moving rats for determination of plasma LH, FSH and PRL concentrations. In Expt. II, Expt. I was repeated using cathodal current and collecting blood samples hourly from 13.00 to 18.00 h. In both experiments the animals were sacrificed on the next morning when the occurrence of ovulation was checked. The medial septal area (MSA), medial preoptic area (MPOA), and medial basal hypothalamus (MBH) were dissected and assayed for norepinephrine (NE), dopamine (DA) and 5-hydroxyindoleacetic acid (5-HIAA) content. Experiment III was performed in order to test if a hormonal discharge occurred immediately after lesion placement. Blood samples were collected immediately before and 15, 30, 60 and 90 min postoperatively (from 11.00 to 12.30 h). Either anodal or cathodal lesions blocked the proestrous surge of LH, FSH and PRL. The hypothesis that the lesions advanced or delayed these hormonal surges was rejected since we found no increases in the hormonal levels from 11.00 to 12.30 or from 13.00 to 18.00 h, and ovulation was not observed on the following morning in the lesioned animals. Since control, sham-operated and missed-lesion groups exhibited LH, FSH and PRL surges and ovulation, this blockage appears to be caused by the destruction of the LC neurons. Also, this blockade was correlated with a decrease in the NA content in the MPOA and MBH, but not in the MSA, whereas the DA and 5-HIAA content were not changed in all groups examined. The results lead us to suggest that the integrity of noradrenergic afferent input from the LC to luteinizing hormone-releasing hormone neurons in the MPOA and MBH is essential for triggering the preovulatory surge mechanisms for gonadotrophins and PRL.

Animals↗
PubMed1992

Different types of norepinephrinergic receptors are involved in preoptic area mediated independent modulation of sleep-wakefulness and body temperature.

The preoptic area is known to regulate sleep-wakefulness and body temperature. It was suggested earlier that though sleep-wakefulness and body temperature may affect each other, the preoptic area mediated influence on those two physiological phenomena is likely to be independent of alteration in each other. Since intrapreoptic area norepinephrine could modulate both those functions, study of that system was undertaken. It was hypothesized that since the preoptic area has different types of norepinephrinergic receptors (viz. alpha 1, alpha 2 and beta), independent modulation of those two functions was probably due to activation or inactivation of separate receptors. Hence, the effects of different agonist and antagonist of those receptors individually as well as in combination into the preoptic area were studied on those two functions in freely moving rats. The results suggest that norepinephrine induced preoptic area mediated influence on the body temperature is primarily regulated by the alpha 1 receptors while the sleep and wakefulness are regulated by alpha 2 and beta receptors, respectively. The finding should help in explaining several poorly understood observations reported earlier and it suggests that similar phenomena may possibly exist in other system involving other neurotransmitters as well.

Acetamides↗
PubMed1988

Immunohistochemical evidence for synaptic connections between pro-opiomelanocortin-immunoreactive axons and LH-RH neurons in the preoptic area of the rat.

Connections between adrenocorticotropic hormone (ACTH)-immunoreactive neurons in the arcuate nucleus and the preoptic area were studied in the female rat. ACTH-immunopositive terminals were observed in the medial preoptic area in contact with dendritic shafts, while in the ventrolateral preoptic area the majority of ACTH-immunoreactive synapses were found on dendritic spines. Double-label electron microscopic immunocytochemistry using peroxidase and avidin-ferritin as contrasting electron-dense markers revealed numerous synaptic contacts between ACTH-immunopositive boutons and luteinizing hormone-releasing hormone (LH-RH)-immunoreactive dendritic shafts in the medial preoptic area. Following injection of horseradish peroxidase (HRP) into the medial preoptic area, retrogradely HRP-labeled perikarya were observed throughout the arcuate nucleus. Double-staining experiments revealed that a proportion of these retrogradely labeled cells, in the ventromedial arcuate nucleus, are also immunoreactive for ACTH. These results suggest that pro-opiomelanocortin peptide-producing neurons in the ventromedial arcuate nucleus project to the medial preoptic area. Some of these neurons establish direct synaptic contacts with LH-RH-immunoreactive cells.

Adrenocorticotropic Hormone↗
PubMed1979

Enhancement of immunoreactive somatostatin release into hypophysial portal blood by electrical stimulation of the preoptic area in the rat.

Electrical stimulation of the preoptic area resulted in a significant increase in the secretion rate of immunoreactive somatostatin (IRS) and its concentration in the hypophysial portal blood of urethane-anesthetized rats. In contrast, stimulation of the ventromedial nucleus did not cause any changes in portal immunoreactive somatostatin. The flow rate of portal blood also increased significantly by electrical stimuli to the preoptic area but not to the ventromedial hypothalamus. These findings support the view that the preoptic area plays an inhibitory role in the regulation of GH secretion by increasing the release of somatostatin into hypophysial portal vessels in the rat.

Animals↗
PubMed1996

Developmental profile and regulation of estrogen receptor (ER) mRNA expression in the preoptic area of prenatal rats.

Estrogen, derived from circulating testosterone, masculinizes the developing preoptic area. Expression of estrogen receptors (ERs) within the preoptic area is one requirement for a possible direct action of estrogen in the process of sexual differentiation of this brain region. Using a 35S-labeled riboprobe and in situ hybridization to detect ER mRNA on both film and emulsion-coated slides, we were able to detect ER mRNA within the rat preoptic area by embryonic day 18 (ED 18), coincident with the reported onset of the critical period for testosterone-dependent masculinization of this region. ER mRNA increased significantly between ED 18 and 19 in both sexes, and continued to increase through postnatal day 0 (PND 0 = day of birth) in females, but not males. ER mRNA levels were not significantly greater in females than in males until PND 0. The lack of a sex difference in ER mRNA prenatally, however, appears to be due to an effect of intrauterine neighbors. ER mRNA levels in ED 20 embryos were relatively high in females with female-only neighbors, whereas ER mRNA levels were relatively low, and comparable to males, when the in utero neighbors included one or more males. Treatment of pregnant dams with diethylstilbestrol or with tamoxifen did not significantly alter ER mRNA levels in the preoptic area of the embryos. Although these results suggest that ER mRNA expression is subject to hormonal regulation prenatally, the relevant hormone was not identified.

Animals↗
PubMed2003

Rapidly activated microglial cells in the preoptic area may play a role in the generation of hyperthermia following occlusion of the middle cerebral artery in the rat.

Postischemic hyperthermia occurs after the occlusion of the middle cerebral artery (MCAO) with an intraluminal filament in rats. The cause of hyperthermia is presumed to be damage to the preoptic area, which is one of the temperature-regulatory centers of the hypothalamus. In the present study, reactions of microglial cells and astrocytes in the preoptic area were examined during the first 6 h following transient MCAO. Microglial cells and astrocytes were visualized with immunohistochemistry using antibodies against the CR3 complement receptor and the glial fibrillary acidic protein, respectively. One hour after the occlusion, activated microglial cells were observed in both the medial and lateral preoptic areas ipsilaterally, and in the medial preoptic area contralateral to the infarct. Following reperfusion, the activation of microglial cells decreased in the medial preoptic area of both hemispheres, and in the lateral preoptic area there was a loss of immunoreactive microglial cells. Fragmentation of astrocytic processes was detected in the lateral preoptic area, while in the ipsilateral medial preoptic area a moderate swelling was observed. Immunohistochemistry with an antibody against interleukin-1beta (IL-1beta) revealed scattered immunoreactive cells in both the ipsilateral and the contralateral medial preoptic area 2 h after the MCAO. Our results show that microglial activation in the preoptic area coincides with postischemic hyperthermia. However, an exclusive role for IL-1beta in the generation of hyperthermia is unlikely, and other factors are probably also responsible for postischemic hyperthermia.

Animals↗
PubMed2002

Effect of ambient temperature on brain temperature and sleep-wakefulness in medial preoptic area lesioned rats.

The changes in brain temperature and sleep-wakefulness were studied in rats during their exposure to different ambient temperatures of 18 degrees C, 24 degrees C and 30 degrees C, before and after N-methyl D-aspartic acid lesion of the medial preoptic area. The medial preoptic area lesion produced a decrease in sleep, and increase in brain temperature except at 30 degrees C. Increase and decrease in brain temperature with slow wave sleep and paradoxical sleep respectively, were observed both in normal and lesioned rats. Sleep-wakefulness and brain temperature cycle durations were increased and their frequencies decreased at higher ambient temperature in normal rats. After the medial preoptic area lesion, sleep-wakefulness cycle duration was decreased and frequency increased at 30 degrees C. There was no significant change in brain temperature cycles at higher ambient temperature in lesioned rats. The medial preoptic area, in normal rats, possibly interlinks the neuronal circuits involved in regulating brain temperature and sleep-wakefulness cycles. The medial preoptic area is essential for increasing the sleep-wakefulness cycle duration with higher ambient temperature. The possible contribution of the increased brain temperature variation in producing sleep-wakefulness changes cannot be ruled out. The results of the study show that this area may serve as a fine tuning mechanism which helps to interlink the sleep-wakefulness with the thermoregulation.

Analysis of Variance↗
PubMed1991

Sexually dimorphic distribution of neurotensin/neuromedin N mRNA in the rat preoptic area.

Neurotensin release from estrogen-responsive neurons in the rostral preoptic area of the female rat may play an important role in triggering preovulatory secretion of gonadotropin-releasing hormone on proestrus. We investigated the possibility of sexually differentiated biosynthesis of neurotensin in the rostral preoptic area, using in situ hybridization histochemistry to detect neurotensin/neuromedin N (NT/N) mRNA in adult male rats and adult female rats at proestrus and the first day of diestrus. In sections through the anteroventral periventricular nucleus (AVPv), the number of labeled cells in proestrous females was four times that in males. Diestrus females exhibited half the number of labeled cells present at proestrus, and there was evidence for a significant correlation between circulating estradiol level and number of labeled cells in the AVPv. In the rostral portion of the medial preoptic nucleus (MPN), two contiguous groups of labeled cells were especially prominent. One group, in the medial half of the MPN, was located closer to the midline in females than in males and displayed greater labeling in males than in females. Furthermore, labeling in the rostral MPN was greater at proestrus than at diestrus. These results indicate that biosynthesis of neurotensin and neuromedin N in the rostral preoptic area may be sexually differentiated and, in the female, may vary across the estrous cycle in parallel with circulating estradiol levels, consistent with the view that neurotensin neurons in this area are involved in the regulation of preovulatory secretion of gonadotropin-releasing hormone. The sex- and region-specific expression of NT/N mRNA in the rostral preoptic area suggests functional heterogeneity of neurotensin neuronal populations in this area and implies complex regulation of NT/N gene expression in the rat brain.

Animals↗
PubMed2005

Isoflurane increases norepinephrine release in the rat preoptic area and the posterior hypothalamus in vivo and in vitro: Relevance to thermoregulation during anesthesia.

General anesthetics modulate autonomic nervous system function including thermoregulatory control, which resides in the preoptic area of the anterior hypothalamus. However, the mechanism by which anesthetics modulate hypothalamic function remains unknown. We hypothesized that isoflurane increases norepinephrine release in the preoptic area and in the posterior hypothalamus causing hypothermia during anesthesia. To test this hypothesis, we performed a series of in vivo and in vitro studies in rats. In vivo studies: 1) Norepinephrine release was measured by microdialysis in the preoptic area or the posterior hypothalamus (n=9 each) before, during (30 min), and after (50 min) rats were anesthetized with 2% isoflurane. 2) In five rats, blood gases and arterial pressure were measured. 3) Body temperature changes (n=6 each) were measured after prazosin (0, 0.05, 0.5 microg), norepinephrine (0, 0.1, 1.0 microg), or 0.5 microg prazosin with 1.0 microg norepinephrine injection into the preoptic area. In vitro study: Norepinephrine release was measured from anterior or posterior hypothalamic slices (n=10 each) incubated with 0, 1, 2, or 4% isoflurane in Ca2+-containing buffer or with 4% isoflurane (n=10) in Ca2+-free buffer. Data were analyzed with repeated measures or factorial ANOVA and Student-Newman-Keuls tests. P<0.05 was significant. During anesthesia, norepinephrine release in the preoptic area was increased approximately 270%, whereas the release in the posterior hypothalamus remained unchanged. During emergence, posterior hypothalamic norepinephrine release increased by approximately 250% (P<0.05). Rectal temperature changes correlated with norepinephrine release from the preoptic area. Norepinephrine in the preoptic area enhanced isoflurane-induced hypothermia, while prazosin reversed it. Norepinephrine release from anterior hypothalamic slices increased at all isoflurane concentrations, but only at the highest concentration in posterior hypothalamic slices. Under Ca2+-free conditions, 4% isoflurane increased norepinephrine from both regions. These results suggest that augmentation of norepinephrine release in the preoptic area is responsible for hypothermia during general anesthesia.

Anesthesia↗
PubMed2003

Direct evidence of facilitative actions of dopamine in the medial preoptic area on reflexive and noncontact erections in male rats.

PURPOSE: We examined the effects of alterations of the extracellular dopamine level in the medial preoptic area on 2 erectile contexts, namely reflexive and noncontact erections, in male rats. MATERIALS AND METHODS: The extracellular dopamine level was measured in the medial preoptic area after administering the dopamine reuptake inhibitor bupropion hydrochloride (Sigma Chemical Co., St. Louis, Missouri) into the same area through a micro-dialysis tube. We measured the frequency and latency of reflexive erections, and the frequency of noncontact erection during infusion of bupropion. RESULTS: Administration of 10 mM. bupropion was associated with significant elevation in the extracellular dopamine level in the medial preoptic area. Bupropion (1 mM.) and Ringer's solution did not induce significant alterations in dopamine in the medial preoptic area. The number of reflexive erections significantly increased and erection latency decreased during infusion of 10 mM. bupropion into the medial preoptic area. The number of noncontact erections was also increased by administering 10 mM. of drug. CONCLUSIONS: The altered dopamine level in the medial preoptic area affected 2 distinct penile erectile contexts, suggesting that the dopamine levels in the medial preoptic area may be involved in the regulation of erection. These results may have important implications for the central regulation of penile erection.

Animals↗
PubMed1998

Effects of parenterally administered triazolam on sleep in rats with lesions of the preoptic area.

In previous work we have reported that microinjections of triazolam or pentobarbital into the medial preoptic area of the anterior hypothalamus produce a hypnotic effect. This finding raised the possibility that the sleep-enhancing actions after systemic administration of these compounds might be mediated by hypnogenic mechanisms in the preoptic area. The current study examined whether sleep enhancement by triazolam requires the anatomic integrity of the preoptic area. Nine rats with histologically confirmed lesions of the preoptic area induced by ibotenic acid (2.5 microg/microl in 0.4 microl), and 10 rats that had undergone a sham lesion procedure, had 2-h sleep studies that confirmed that by day 5 measures of total sleep time and sleep latency had returned to preintervention values. Rats were then given triazolam 0.8 mg/kg or vehicle intraperitoneally in counterbalanced order, on days 7 and 9 postlesion, in an environment with an ambient temperature of 25 degrees C. Following injections at 1000 h, in conditions in which lights were on from 0800-2000 h, 2-h sleep studies were performed. In the lesioned rats, triazolam significantly decreased sleep latency and increased total sleep time, primarily by increasing NREM sleep, whereas injections of vehicle did not. In summary, parenterally administered triazolam was found to have hypnotic effects in rats who were 1 week post-preoptic area lesion. These data are interpreted in light of previous evidence of redundancy of sleep-regulating mechanisms in the nervous system.

Animals↗
PubMed1994

Role of lateral preoptic area alpha-1 and alpha-2 adrenoceptors in sleep-wakefulness and body temperature regulation.

The preoptic area is anatomically divided into medial and lateral portions and both are involved in the regulation of sleep-wakefulness and body temperature. We have recently reported the specific role of the adrenoceptors, present in the medial preoptic area, in the regulation of those functions. In this study an attempt was made to investigate the specific participation and contribution of the lateral preoptic area alpha-1 and alpha-2 adrenoceptors in the regulation of sleep-wakefulness and body temperature. Sleep-wakefulness and rectal temperature were simultaneously recorded in freely moving rats, both during day and night, under normal condition and after bilateral local microinjection of either agonist or antagonist of alpha-1 and alpha-2 adrenoceptors into the lateral preoptic area. The results suggest that the lateral preoptic area alpha-2 adrenoceptors are predominantly involved in the regulation of sleep-wakefulness whereas alpha-1 adrenoceptors are more effective in thermoregulation.

Adrenergic alpha-1 Receptor Agonists↗
PubMed1991

Thalamic and midbrain auditory projections to the preoptic area and ventral hypothalamus in the green treefrog (Hyla cinerea).

Iontophoretic injections of horseradish peroxidase (HRP) into either the preoptic area or ventral hypothalamus of the green treefrog, (Hyla cinerea), demonstrated inputs from thalamic and midbrain auditory nuclei. In a pattern similar to that seen in Rana catesbeiana and Rana pipiens, the central thalamic and secondary isthmal nuclei were found to provide heavy input to the ventral hypothalamus. Additionally, a lighter input from the anterior thalamic nucleus was seen. In contrast, the preoptic area receives a major input from the anterior thalamic and secondary isthmal nuclei, and possibly a sparse input from the central thalamic nucleus. These results suggest that in treefrogs multimodal and auditory information may reach the preoptic area and ventral hypothalamus, two regions involved in endocrine regulation and the control of reproductive behavior, via largely separate major pathways from the thalamus combined with a common midbrain input. Furthermore, the ventral hypothalamus receives heavy input from the preoptic area, lateral amygdala, suprachiasmatic nucleus, anterior entopeduncular nucleus, and a lighter input from the striatum. Nonauditory afferents to the preoptic area originate in the medial and lateral septal nuclei, medial pallium, and the dorsal-, lateral-, and ventral hypothalamus. The preoptic area and ventral hypothalamus are reciprocally connected.

Animals↗
PubMed1990

[Modulating effect of estradiol on the sensitivity of the preoptic area neurons to noradrenaline].

Sensitivity of the preoptic area neurons to norepinephrine before and after application of estradiol was investigated. The obtained results show that estradiol influences neuron sensitivity. Microiontophoretic application of norepinephrine followed the estradiol into the preoptic area and increased the activity of single neurons in the majority of experiments. This modulation effect of estradiol was more pronounced at the stage of proestrus.

Animals↗
PubMed1998

Efferent projection from the preoptic area for the control of non-shivering thermogenesis in rats.

1. To investigate the characteristics of efferent projections from the preoptic area for the control of non-shivering thermogenesis, we tested the effects of thermal or chemical stimulation, and transections of the preoptic area on the activity of interscapular brown adipose tissue in cold-acclimated and non-acclimated anaesthetized rats. 2. Electrical stimulation of the ventromedial hypothalamic nucleus (VMH) elicited non-shivering thermogenesis in the brown adipose tissue (BAT); warming the preoptic area to 41.5 C completely suppressed the thermogenic response. 3. Injections of d, l-homocysteic acid (DLH; 0.5 mM, 0.3 microliter) into the preoptic area also significantly attenuated BAT thermogenesis, whereas injections of control vehicle had no effect. 4. Transections of the whole hypothalamus in the coronal plane at the level of the paraventricular nucleus induced rapid and large rises in BAT and rectal temperatures. This response was not blocked by pretreatment with indomethacin. The high rectal and BAT temperatures were sustained more than 1 h, till the end of the experiment. Bilateral knife cuts that included the medial forebrain bundle but not the paraventricular nuclei elicited similar rises in BAT and rectal temperatures. Medial knife cuts had no effect. 5. These results suggest that warm-sensitive neurones in the preoptic area contribute a larger efferent signal for non-shivering thermogenesis than do cold-sensitive neurones, and that the preoptic area contributes a tonic inhibitory input to loci involved with non-shivering thermogenesis. This efferent inhibitory signal passes via lateral, but not medial, hypothalamic pathways.

Acclimatization↗
PubMed2006

Tonic activity of alpha1 adrenergic receptors of the medial preoptic area contributes towards increased sleep in rats.

Several studies have suggested that noradrenergic afferents to the medial preoptic area might be involved in hypnogenesis and in lowering the body temperature, and that the alpha1 adrenergic receptors might be mediating these responses. This study was undertaken to find out the changes in sleep-wakefulness and body temperature in rats, when these adrenergic receptors of the medial preoptic area are blocked by alpha1 selective antagonist, prazosin. Adult male Wistar rats were chronically implanted with electrooculogram, electroencephalogram and electromyogram electrodes for sleep-wakefulness assessment, and a bilateral guide cannula for microinjection of prazosin at the medial preoptic area. A radio-transmitter was implanted in the abdomen for telemetric measurement of body temperature in four groups of rats. Sleep-wakefulness was also assessed telemetrically in four other groups of rats. Sleep-wakefulness recordings from these rats were done in a specialized chamber, where they could move about freely and select the ambient temperature which they prefer. Prazosin induced a dose dependent increase in wake period and in body temperature, when microinjected into the medial preoptic area. Results suggest that preoptic alpha1 adrenergic receptors mediate hypnogenic and hypothermic responses. It is proposed that the noradrenergic afferents to the medial preoptic area, by tonic activation of alpha1 adrenergic receptors, contribute towards increase in sleep especially during the daytime.

Adrenergic alpha-Antagonists↗
PubMed1998

The effect of anabolic-androgenic steroids on aromatase activity and androgen receptor binding in the rat preoptic area.

The level of aromatase in the preoptic area of rats is transcriptionally regulated through a specific androgen-receptor mediated mechanism and can be used as a measure of central androgenic effect. Therefore, several commonly abused anabolic-androgenic steroids (AAS) were tested for their ability to induce aromatase activity in the preoptic area of castrated rats. In addition, we determined the relative binding affinities of these compounds for the androgen receptor, as well as their ability to bind androgen receptor in vivo following subcutaneous injections. All of the AAS compounds tested significantly stimulated POA aromatase activity above castrate levels. The compounds that produced the greatest stimulation of aromatase activity were those that bound most avidly to the androgen receptor in vitro (i.e., testosterone, dihydrotestosterone and nandrolone). In contrast, the 17alpha-alkylated compounds that were tested (stanozolol, danazol, methandrostenolone) modestly stimulated aromatase and were weak competitors for the androgen receptor. The subcutaneous injection of AAS compounds increased the concentrations of occupied nuclear androgen receptors in the brain, but the magnitude of effect was not related to their potency for inducing aromatase or their relative binding affinity for the androgen receptor suggesting that androgen receptor occupancy in POA is not correlated with the action of androgen on aromatase. The present results help explain the behavioral effects of AAS compounds in rats.

Anabolic Agents↗
PubMed1996

The role of apoptosis in sexual differentiation of the rat sexually dimorphic nucleus of the preoptic area.

The sexually dimorphic nucleus of the preoptic area (SDN-POA) in the rat hypothalamus is larger in volume in males than in females due to a larger number of cells in the nucleus. Although the SDN-POA, and its development, have been extensively studied, the actual mechanism of its sexual differentiation has not been established. The results of previous studies have not supported a role for gonadal steroids in the regulation of neurogenesis or the determination of the migratory pathway perinatally. In this study, the role of cell death in the development of the sexual dimorphism in the SDN-POA was investigated using in situ end-labeling to visualize fragmented DNA in apoptotic cells. In the experiments described here, the incidence of apoptosis was determined in part of the SDN-POA, the central division of the medial preoptic nucleus (MPNc), over the first 13 days postnatally in male and female rats. There was a sex difference in the incidence of apoptosis in the MPNc between postnatal days 7 and 10; the incidence was higher in females. The role of testosterone (T) in regulating the incidence of apoptosis in the developing MPNc was examined in neonatally castrated males following T or vehicle injection. Testosterone had a profound inhibitory effect on the incidence of apoptosis between days 6 and 10. In a control region within the lateral preoptic area, there was no sex difference in the incidence of apoptosis, nor was there an effect of T. Thus, the data indicate that the regulation of apoptosis by T is one mechanism involved in the sexual differentiation of the SDN-POA.

Animals↗