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PubMed1994

Changes in sleep-wakefulness after kainic acid lesion of the preoptic area in rats.

The role of the preoptic area (POA) neurons in the regulation of sleep-wakefulness (S-W) has been investigated in this study. The cell-specific neurotoxin, kainic acid (KA), was injected (0.8 microgram in 0.2 microliter) intracerebrally for lesioning of the POA. S-W was assessed (on the basis of EEG, EMG, and EOG recordings) for a day before bilateral lesion of the POA, and for 3 weeks after the lesion. There was an increase in wakefulness, and a decrease in all the stages of sleep after KA lesion of the POA. The reduction in deep slow wave sleep (S2) and REM sleep (PS) were more marked than light slow wave sleep (S1), and these had not shown any recovery even after 3 weeks of lesion. Two days after the lesion, the reduction in sleep was much more marked during the daytime than at night. There was an increase in locomotor activity, especially during the daytime, though it was only statistically significant on the 6th and the 10th day after the lesion. This study shows that the POA neurons are involved in the induction and maintenance of sleep. The lesion did not have a long lasting effect on the circadian distribution of sleep but the changes in locomotor activity seem to persist for a longer period.

Animals↗
PubMed2004

Nitric oxide mediates glutamate-evoked dopamine release in the medial preoptic area.

Dopamine (DA) release in the medial preoptic area (MPOA) of the hypothalamus is an important facilitator of male sexual behavior. The presence of a receptive female increases extracellular DA in the MPOA, which increases further during copulation. However, the neurochemical events that mediate the increase of DA in the MPOA are not fully understood. Here we report that glutamate, reverse-dialyzed into the MPOA, increased extracellular DA, which returned to baseline after the glutamate was removed. This increase was prevented by co-administration of the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (L-NAME), but not by the inactive isomer, Nw-nitro-d-arginine methyl ester (D-NAME). In contrast, extracellular concentrations of the major metabolites of DA were decreased by glutamate, suggesting that the DA transporter was inhibited. These decreases were also inhibited by L-NAME, but not D-NAME. These results indicate that glutamate enhances extracellular DA in the MPOA, at least in part, via nitric oxide activity. Therefore, glutamatergic stimulation of nitric oxide synthase may generate the female-induced increase in extracellular DA in the MPOA, which is important for the expression of male sexual behavior.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2001

Evidence of sex hormone binding globulin binding sites in the medial preoptic area and hypothalamus.

We have demonstrated a high density of both radiolabeled progesterone and estradiol conjugated to bovine serum albumin binding sites in the medial preoptic area and hypothalamus. Infusions of sex hormone binding globulin into the medial preoptic area of rats increased their female sexual receptivity similarly to the effect of estradiol conjugated to bovine serum albumin, suggesting sex hormone binding globulin acts at binding sites for estradiol conjugated to bovine serum albumin. In this study sex hormone binding globulin was used to displace radiolabeled progesterone conjugated to bovine serum albumin from plasma membrane fractions from the medial preoptic area-anterior hypothalamus and medial basal hypothalamus of ovariectomized rats injected with either 5 microg estradiol benzoate or sesame oil vehicle. We found that sex hormone binding displaced radiolabeled progesterone conjugated to bovine serum albumin in both areas and that in vivo estradiol treatment greatly increased the relative displacement by sex hormone binding globulin in the medial preoptic area-anterior hypothalamus. We interpret these data as indicating the presence of sex hormone binding globulin receptors in brain plasma membranes and further suggest that endogenous steroid conditions may alter these receptors.

Animals↗
PubMed2001

Noradrenergic projections from the A1 field to the preoptic area in the brain of the ewe and Fos responses to oestrogen in the A1 cells.

Previous studies have shown that there is a population of noradrenergic cells in the caudal A1 field of the brainstem of the ewe that contain oestrogen receptors and project to the preoptic area, where gonadotrophin releasing hormone (GnRH) neurones are located. There are some discrepancies in the literature regarding the extent of this projection and the location of the cells in the A1 region. The issue has been a focus of attention because the positive feedback response to oestrogen that causes the ovulatory GnRH/luteinizing hormone surge may originate from this brainstem region. The aim of the present study was to determine the extent of the projections to the preoptic area and to determine whether the caudal A1 cells are activated by oestrogen. Eleven ovariectomized ewes received an injection of the retrograde tracer FluoroGold into the preoptic hypothalamus and four of these also received an i.m. injection of oestrogen 2 h before tissue collection. A further three sheep received i.m. oil injections to act as controls for those receiving oestrogen. Dopamine-beta-hydroxylase (DBH)-positive, retrogradely labelled cells were found within the A1 field in sheep that received preoptic FluoroGold injections. Cells in the vicinity of the A2 and A6 fields, that were retrogradely labelled with FluoroGold, were not DBH-positive. Thus, cells in the A1 field provide a direct noradrenergic projection to the preoptic area and may be involved in the control of the secretion of GnRH in this species. Cells that project to the preoptic hypothalamus from more rostrally located areas of the brainstem are not noradrenergic. In the animals that received oestrogen, double-labelling immunohistochemistry was performed throughout the A1 field for FluoroGold, DBH and Fos. DBH cells of the A1 field expressed Fos only in the oestrogen-treated animals and not in the oil-treated animals. There was a decline in the number of DBH cells that were retrogradely labelled from the caudal region of A1 towards obex. There was a similar gradient in the number of cells that were double-labelled for Fos and FluoroGold. We conclude that there is a population of noradrenergic cells in the caudal A1 field that project to the preoptic area; this is a larger group of cells than previously reported. Oestrogen elicits an acute Fos response in these cells, which may be involved in the time-delayed positive feedback response on GnRH cells. The caudal-to-rostral gradient in the labelling with FluoroGold and Fos in DBH-positive cells is similar to that seen previously for oestrogen receptor in DBH-positive cells in the A1 field.

Animals↗
PubMed1984

Involvement of the telencephalic hemispheres and the preoptic area in sexual behavior of the male goldfish, Carassius auratus: a brain-lesion study.

To locate the brain areas involved in sexual behavior, the effects on male sexual behavior of localized electrolytic lesions in various parts of the telencephalic hemispheres and the preoptic area and of gross ablations of parts of the telencephalic hemispheres were examined in goldfish. All three patterns of male sexual behavior examined (following, butting , and spawning) were severely impaired after bilateral lesions confined to the area ventralis telencephali pars supracommissuralis and/or posterior parts of the area ventralis telencephali pars ventralis (Vs- pVv ), the nucleus preopticus periventricularis (NPP), the lateral forebrain bundle ( LFB ), or the medial forebrain bundle (MFB). On the other hand, sexual behavior was almost unaffected after bilateral ablations of the anterior part or lateral and dorsal parts of the telencephalic hemispheres (AT or LT-DT). Bilateral lesions confined to the area ventralis telencephali pars dorsalis (Vd), the area ventralis telencephali pars postcommissuralis (Vp), the area dorsalis telencephali pars centralis (Dc), the nucleus preopticus (NPO), or the lateral preoptic area (LPA) also had almost no effect on sexual behavior. These results indicate that a particular site in the ventral part of the telencephalic hemispheres (Vs- pVv ) and the anterior part of the preoptic area (NPP) play important roles in the sexual behavior of male goldfish. It was suggested that facilitatory influences from these areas are transmitted through the LFB and/or the MFB.

Animals↗
PubMed2000

The substrate for brain-stimulation reward in the lateral preoptic area. I. Anatomical mapping of its boundaries.

Given the putative role of the lateral preoptic area as a primary contributor of the cell bodies of origin of the descending pathway linking a subset of lateral hypothalamic and ventral tegmental area reward neurons, the distribution of self-stimulation sites in this structure was mapped in 22 animals using moveable electrodes and threshold procedures. Ninety-seven electrode sites were evaluated with placements ranging from just rostral to the midline convergence of the anterior commissure back to the transition zone between the lateral preoptic and lateral hypothalamic areas; of these, roughly 2/3 supported self-stimulation which was widely observed throughout the lateral preoptic area and medial forebrain bundle. In general, self-stimulation thresholds obtained from lateral sites were most stable, and progressively so approaching more caudal regions. Examination of the slopes of the period/current trade-off functions revealed a tendency for higher values in lateral and caudal sites; in contrast, dorsoventral excursions did not influence these estimates. Taken together, these data provide support for the notion that the substrate for brain-stimulation reward in the lateral preoptic area has a relatively homogeneous distribution that is more diffusely organized than that found in reward sites activated further caudally in the medial forebrain bundle.

Animals↗
PubMed1977

A daily neural signal for luteinizing hormone release in the untreated ovariectomized rat: changes in gonadotropin-releasing hormone content of the preoptic area and hypothalamus throughout the day.

Gonadotropin-releasing hormone (GnRH) content of preoptic areas (POA) and hypothalami, and serum gonadotropins of rats ovariectomized six weeks earlier were measured throughout the day in two experiments. In the first, rats were decapitated at 2 h intervals between 0800 and 1800 h. The entire preoptic-hypothalamic region was removed and extracted for radioimmunoassay (RIA) of GnRH. Serum gonadotropins measured by RIA were highly variable but mean concentrations were not significantly different throughout the day. However, preoptic hypothalamic content of GnRH declined markedly between 1000 and 1200 h. In the second experiment, 75 rats were divided into three groups and were untreated or were implanted sc with empty Silastic capsules or capsules containing estradiol-17beta (E2). Two days later, groups of five rats from each of the three treatment groups were decapitated at 0800, 1100, 1400, 1700 and 2000 h. The preoptic area was separated from the hypothalamus by a transverse cut at the caudal aspect of the optic chiasm. POA and hypothalamic content of GnRH correlated well (r=0.74, P less than 0.001, n=75). Two-way analysis of variance failed to reveal any effect of treatment on the GnRH content in either the POA or hypothalamus. GnRH content of both regions decreased significantly between 1100 and 1700h regardless of whether E2 was administered. In striking contrast, gonadotropin surges occurred in the late afternoon only in the E2-treated rats. Serum GnRH was undetectable (less than 5 pg/ml) in all groups of animals. These experiments demonstrate that in the untreated ovariectomized rat GnRH content of the POA and hypothalamus decreases during the early afternoon. This study supports the concent of a daily neural signal for LH release and that E2 is necessary for expression of the daily LH surge in the ovariectomized rat.

Animals↗
PubMed1985

Behavioral effects of vasopressin and oxytocin within the medial preoptic area of the golden hamster.

Arginine-vasopressin (AVP) microinjected into the medial preoptic area (MPOA) induces flank marking behavior, a form of olfactory communication, in the golden hamster. When exposed to the odors of conspecifics flank marking behavior occurs naturally in association with grooming of the flank gland region. The present study examined whether microinjection of AVP, oxytocin (OXY) and other biologically active peptides into the medial preoptic area (MPOA), lateral cerebroventricle (LV) or the ventromedial or lateral hypothalamus (VMH-LH) would elicit flank gland grooming. Microinjection of AVP and OXY produced 2-3 times more flank gland grooming when microinjected into the MPOA than saline, neurotensin or angiotensin II. Injection of AVP into the LV and VMH-LH produced significantly less flank gland grooming than when injected into the MPOA.

Angiotensin II↗
PubMed1994

Oxytocin activates the postpartum onset of rat maternal behavior in the ventral tegmental and medial preoptic areas.

Oxytocin binding (Bmax) was found to be higher in the ventral tegmental area (VTA) and the medial preoptic area (MPOA) at midparturition compared with Pregnancy Days 15-17 or Postpartum Days 5-7 in rat dams. Pup retrieval and assuming a nursing posture over pups were blocked in parturient dams by infusions of an oxytocin antagonist into the VTA or MPOA and by infusions of a vasopressin (V1) antagonist into the MPOA. These results implicate oxytocin in the VTA and MPOA and vasopressin in the MPOA, as well as a parturition-associated rise in oxytocin binding in these sites in the postpartum activation of maternal behavior.

Animals↗
PubMed1991

Medial preoptic area affects sleep-wakefulness independent of associated body temperature change in free moving rats.

Sleep-wakefulness and body temperature may modulate each other. Though both the functions are influenced by the medial preoptic area, the mechanism of action was not clear. This study was aimed at finding out whether the tonic influence of the medial preoptic area on sleep-wakefulness was independent of or secondary to simultaneous change in body temperature. The effects of inactivation of the area by a long acting local anaesthetic, marcain, on those physiological functions were investigated during the night and the day in freely moving rats. Though medial preoptic area influenced sleep-wakefulness and body temperature simultaneously, the effect on the latter was prolonged. The results suggest that the influence on sleep-wakefulness is unlikely to be associated with simultaneously changing body temperature. However, this study fails to differentiate whether the observed effects were due to inactivation of the cell body or the fibers passing through the area.

Animals↗
PubMed1993

Estrogen-receptor immunoreactivity in hamster brain: preoptic area, hypothalamus and amygdala.

The distribution of estrogen-receptor containing cells in the preoptic area, hypothalamus and amygdala of female Syrian hamster brain was studied by immunocytochemical methods. Dense populations of estrogen-receptor immunoreactive (ER-IR) cells were found in the medial preoptic area, the bed nucleus of the stria terminalis, amygdala, ventral and lateral parts of the hypothalamus, and the arcuate nucleus. Injection of estradiol caused a decrease in estrogen-receptor immunoreactivity (ERIR) containing cells within one hour, a decrease that may reflect a change in the ability of the occupied estrogen receptor to bind the particular antibody (H222) used rather than down-regulation of the estrogen receptor. Our findings on the distribution of estrogen-receptor containing cells in these areas using an immunocytochemical technique are consistent with and extend the findings of others using autoradiographic and in vitro binding techniques to study estrogen receptor distribution in hamster brain.

Amygdala↗
PubMed1996

The hypothalamic ventromedial nucleus sends a met-enkephalin projection to the preoptic area's periventricular zone in the female rat.

The female but not the male rat possesses a dense network of methionine enkephalin (m-Enk) fibers in the periventricular zone of the preoptic area (pePOA). The potential source of these fibers was determined by injection of the tracer fluorogold, FAu, into the preoptic area of adult female rats. Twenty-four hours before they were killed, the rats were administered colchicine (intraventricularly) to enable immunocytochemical visualization of m-Enk cells. Upon examination of the brains with fluorescence microscopy, double-labeled cells showing fluorogold and immunofluorescence for m-Enk were consistently observed in the preoptic area, the ventrolateral division of the ventromedial nucleus of the hypothalamus (VMHvl) and nearby medial tuberal area (MTA), the arcuate nucleus, periventricular area of the hypothalamus, perifornical area, and dorsomedial nucleus of the hypothalamus. A series of lesion and knife cut experiments using glass, Halasz, and wire knives determined that the pePOA m-Enk fibers arose from the hypothalamus, near or within the VMH. Ibotenic acid lesions further determined that the source of the m-Enk projection was the VMHvl with a possible additional contribution from the MTA.

Animals↗
PubMed1985

An HRP study of afferent connections of the supracommissural ventral telencephalon and the medial preoptic area in himé salmon (landlocked red salmon, Oncorhynchus nerka).

The supracommissural ventral telencephalon and the medial preoptic area have been shown to play important roles in the sexual behavior of himé salmon (landlocked red salmon, Oncorhynchus nerka). In the present study, the sites of neurons projecting to these regions were examined by means of the retrograde horseradish peroxidase (HRP) tracing method. The morphology of neurons in these sites of origin was also studied by means of the Golgi method. The nucleus preopticus periventricularis and the rostral part of nucleus preopticus (NPP-rNPO) received bilateral projections from the middle parts of the area ventralis telencephali pars ventralis (Vv) and the area ventralis telencephali pars dorsalis (Vd), NPP and lateral part of the preoptic area (LPOA), ipsilateral projections from the caudal part of Vv, nucleus anterioris periventricularis (NAPv), nucleus ventromedialis thalami (NVM) at the level of the posterior commissure, nucleus lateralis tuberis pars medialis (NLTm), nucleus anterior tuberis (NAT), nucleus saccus vasculosus (NSV), nucleus recessus posterioris (NRP) and midbrain tegmentum (TG), and a projection from the nucleus posterior tuberis (NPT), which is situated on the midline of the brain. The area ventralis telencephali pars supracommissuralis and neighboring caudal ventral telencephalon (Vs-cV) received ipsilateral projections from almost all parts of the Vv, the middle and caudal parts of Vd, almost all parts of the NNP, the NPO at the level between the habenula and the posterior commissure, and the rostral part of the nucleus dorsomedialis thalami (NDM). The Vs-cV also received a projection from NPT. These findings seem to give anatomical bases for understanding the neural mechanisms involved in sexual behavior as well as neuroendocrine functions.

Afferent Pathways↗
PubMed1988

Increase of multiple unit activity during slow wave sleep in the cat preoptic area.

Multiple unit activities (MUA) in 307 brainstem sites were recorded by chronically implanted electrodes in cats, using a polygraph with 4 channel MUA recording units. During transition from waking to slow wave sleep, at 15 sites including the medial preoptic area (11), the diagonal band of Broca (2) and medial anterior hypothalamic area (2), consistently earlier increase of MUA in discharge rate was observed, while MUA in other areas decreased. Also, at 13 sites in these areas, a decrease in discharge rate was demonstrated during paradoxical sleep. These findings suggest a close relationship between the preoptic area and sleep mechanisms, supporting a notion that an active site for induction of slow wave sleep may reside in the preoptic area.

Action Potentials↗
PubMed2004

FOS expression in orexin neurons following muscimol perfusion of preoptic area.

Unilateral microdialysis-perfusion of the preoptic area with 50 microM muscimol decreased the sleep period of rats to less than 3% of the baseline value over a 90 min period before death (p = 0.018 by Wilcoxon signed-rank test). These rats showed the expression of FOS in 36% of the orexin neurons located in the perifornical/lateral hypothalamic areas on the side ipsilateral to the perfusion site, but in only 3% of the orexin neurons on the side contralateral to it (p = 0.018 by Wilcoxon signed-rank test). These results suggest that subpopulations of the preoptic neurons give an inhibitory tone to the activities of the orexin neurons in the perifornical/lateral hypothalamic areas.

Animals↗
PubMed1992

Increased expression of c-fos in the medial preoptic area after mating in male rats: role of afferent inputs from the medial amygdala and midbrain central tegmental field.

Immunocytochemical methods were used to localize the protein product of the immediate-early gene, c-fos, in male rats after exposure to, or direct physical interaction with, oestrous females. Increasing amounts of physical contact with a female, with resultant olfactory-vomeronasal and/or genital-somatosensory inputs, caused corresponding increments in c-fos expression in the medial preoptic area, the caudal part of the bed nucleus of the stria terminalis, the medial amygdala, and the midbrain central tegmental field. Males bearing unilateral electrothermal lesions of the olfactory peduncle showed a significant reduction in c-fos expression in the ipsilateral medial amygdala, but not in other structures, provided their coital interaction with oestrous females was restricted to mount-thrust and occasional intromissive patterns due to repeated application of lidocaine anaesthetic to the penis. No such lateralization of c-fos expression occurred in other males with unilateral olfactory lesions which were allowed to intromit and ejaculate with a female. These results suggest that olfactory inputs, possibly of vomeronasal origin, contribute to the activation of c-fos in the medial amygdala. However, lesion-induced deficits in this type of afferent input to the nervous system appear to be readily compensated for by the genital somatosensory input derived from repeated intromissions. Unilateral excitotoxic lesions of the medial preoptic area, made by infusing quinolinic acid, failed to reduce c-fos expression in the ipsilateral or contralateral medial amygdala or central tegmental field following ejaculation. By contrast, combined, unilateral excitotoxic lesions of the medial amygdala and the central tegmental field significantly reduced c-fos expression in the ipsilateral bed nucleus of the stria terminalis and medial preoptic area after mating; no such asymmetry in c-fos expression occurred when lesions were restricted to either the medial amygdala or central tegmental field. This suggests that afferent inputs from the central tegmental field (probably of genital-somatosensory origin) and from the medial amygdala (probably of olfactory-vomeronasal origin) interact to promote cellular activity, and the resultant induction of c-fos, in the ipsilateral bed nucleus of the stria terminalis and medial preoptic area. The monitoring of neuronal c-fos expression provides an effective means of studying the role of sensory factors in governing the activity of integrated neural structures which control the expression of a complex social behaviour.

Amygdala↗
PubMed2002

GABA release in the medial preoptic area of cyclic female rats.

GABA is a potent regulator of gonadotropin-releasing hormone neurons in the hypothalamus. To determine the profile of GABA release in the medial preoptic area where the gonadotropin surge generator resides, an in vivo microdialysis study was performed in cyclic female rats. The microdialysis samples were collected and sequential blood samples (150 microl each) were also obtained, at 1-h intervals. During estrus and diestrus 1, GABA release in the medial preoptic area was relatively low. A small increase in the GABA release began in the afternoon of diestrus 1 and attained its peak in the morning of diestrus 2, but declined in the afternoon of that day. The GABA release markedly increased from late in the night of diestrus 2 through the morning of proestrus, when it attained its peak, and thereafter it declined sharply until the critical period of proestrus. A distinct preovulatory luteinizing hormone surge was observed in the afternoon of proestrus in all proestrous rats. From these results we suggest that the preovulatory elevation of the GABA release from the night through to the morning of proestrus, followed by a sharp decline, is closely associated with the onset of the preovulatory luteinizing hormone surge in cyclic female rats. The present study is the first to report the 4-day profile of GABA release in the medial preoptic area during the estrous cycle.

Animals↗
PubMed1987

The effects of the age of intracerebroventricular grafts of normal preoptic area tissue upon pituitary and gonadal function in hypogonadal (HPG) mice.

Hypogonadal mice are deficient in the hypothalamic gonadotrophic hormone releasing hormone and as a consequence postnatal testicular development does not occur. Grafting preoptic area tissue from normal mice directly into the hypogonadal third ventricle dramatically reverses the hypogonadism; however, the age of the grafted preoptic area tissue is crucial to the survival and function of the graft. Grafting embryonic tissue (E16-18) resulted in 69% of the hypogonadal mice increasing testis weight some sevenfold within 30 days (5.6 to 35 mg). Postnatal day 1 (P1) tissue grafts elicited a similar rise in testis weight in 77% of recipients, whereas P5 tissue was only successful in 22% of cases. In this experimental group, however, testis weight also increased sevenfold compared with hypogonadal untreated mice. Stimulation of testicular growth in the E16-18 and P1 experimental groups was accompanied by an increase in pituitary gonadotrophic hormone content. P10 tissue did not stimulate testis growth nor was pituitary gonadotrophic hormone control elevated and the majority of grafts failed to survive over the 30 day period of the experiment. The present study has shown that the age of grafted tissue is critical in the restoration of physiological function in hypogonadal mice, and that gonadotrophic hormone releasing hormone neurons from E16-18, P1 and P5 preoptic area grafts that survive the 30 day period of the experiment and whose axons reach the median eminence portal vessels are equipotent in stimulating pituitary gonadotrophin synthesis and secretion.

Age Factors↗