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Effects of hydroxyflutamide in the medial preoptic area or lateral septum on reproductive behaviors in male rats.

We examined whether androgen receptors in the medial preoptic area (MPOA) and lateral septum (LS) are required for the expression of copulation and sexual motivation. Castrated males received testosterone-filled silastic capsules to restore behavior, and were implanted with the antiandrogen hydroxyflutamide (OHF) or blank cannulae. One group was implanted in either the anteroventral MPOA or LS (ANT group). Another group was implanted in the posterodorsal MPOA or LS (POST group). Copulation was tested on days 2, 6, 10, and 14 of OHF exposure; partner preference, a measure of sexual motivation, was tested on day 15. The results showed that sexual behavior was significantly suppressed by OHF in the MPOA of the ANT group, but not the POST group. However, sexual motivation was significantly reduced by OHF in the MPOA of the POST group, but not the ANT group. In the LS, OHF had no effect on sexual behavior and partner preference regardless of implant site. The data suggest site specificity within the MPOA for androgen receptor activation of male reproductive behaviors.

Androgen Antagonists↗

Medial preoptic area and onset of maternal behavior in the rat.

The present series of experiments examined whether the medial preoptic area (MPOA) is involved in the onset of maternal behavior in the rat. Previously, the MPOA had been shown to be important in the maintenance of maternal behavior in the lactating rat. The first experiment investigated whether estradiol benzoate (EB) acts on the MPOA to facilitate the onset of maternal behavior in the 16-day pregnant, hysterectomized, and ovariectomized female rat. Such rats when given EB implants in the MPOA had significantly shorter latencies for the onset of maternal behavior than had females implanted with cholesterol in the MPOA or with EB in the ventromedial hypothalamus, in mammillary bodies, or under the skin. A second experiment showed that estrogen-induced prolactin release was not involved in this facilitation. A third experiment indicated that MPOA lesions disrupt the onset of maternal behavior that is induced by pup stimulation in virgin females. It was concluded that the MPOA is involved not only in the maintenance of maternal behavior but in the hormonally mediated onset of maternal behavior and the onset of maternal behavior induced in virgin females by pup stimulation.

Animals↗

Convergence from the preoptic area and arcuate nucleus to the median eminence in acupuncture and nonacupuncture point stimulation analgesia.

Lesion of the preoptic area (POA) or medial arcuate nucleus (M-HARN) abolished acupuncture analgesia (AA). Potentials in the median eminence (ME) evoked by stimulation of the acupuncture point (AP) were not affected by lesion of either the POA or M-HARN alone, but were abolished by concurrent lesion of both. No analgesia was produced by stimulation of the POA. Analgesia produced by stimulation of the M-HARN was abolished by lesion of the POA, and the abolished analgesia was restored by concurrent stimulation of the POA and M-HARN, hence POA and M-HARN outputs might converge in the ME to produce AA. Similar convergence from the anterior arcuate nucleus (A-HARN) and POA to the ME was observed in analgesia (NAA) produced by stimulation of a nonacupuncture point (NAP). Two pathways diverged from the lateral hypothalamus in the AA afferent pathway and two from the lateral periaqueductal central gray (L-PAG) in the NAA afferent pathway. POA potentials evoked by stimulation of the AP were reversed by naloxone, and those evoked by stimulation of the AP were reversed by dexamethasone. ACTH sensitive sites were found in both the L-PAG and the anterior hypothalamus.

Acupuncture Analgesia↗

Fever produced by the fungus T. beigelii infused into the anterior hypothalamic preoptic area of the rat.

Previously it was reported that a control saline solution infused into the anterior hypothalamic, preoptic area (AH/POA) can induce an intense fever from an unknown source. To avoid such fevers, cerebral dialysis has been proposed as an alternative procedure, although in nearly all experiments on the febrile response, a nonpyrogenic solution is injected, not dialyzed, directly into the AH/POA. The purpose of this study was to determine the: a) possible conditions whereby a control solution can cause an experimental fever; b) putative organisms which may comprise the source of a centrally induced fever; and c) procedures whereby such fevers can be avoided. In twelve adult male Sprague-Dawley rats, an intracerebral cannula for microinjections and a Minimitter temperature transmitter were implanted within the AH/POA and intraperitoneal cavity, respectively. Following recovery, the thermoreactivity of each site in the AH/POA was verified by a microinjection of norepinephrine which typically lowers body temperature (Tb) by 0.5-1.0 degrees C. Two artificial cerebrospinal fluid (CSF) test solutions were used: one exposed to the ambient conditions of the laboratory, and a second prepared under pathogen-free conditions, including filtration, to exclude biological contaminants. A rise in temperature of 0.8-1.0 degrees C within 1.0 h after microinjection, which increased to as high as 3.5 degrees C within 4 h, typically was produced by the contaminated artificial CSF solution. The filtered CSF did not evoke a consistent or reliable rise in Tb of the rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Sexually dimorphic effect of glutamate treatment on cell cycle arrestment of astrocytes from the preoptic area of neonatal rats.

Neurotoxicological studies have indicated that L-glutamate exhibits more pronounced effects on the preoptic area (POA) neurons of male rats than on those of females in the neonatal period. However, no information has previously been available as to whether or not such sexual dimorphism also exists for the effects of glutamate on astrocytes from POA. The present paper reports the differential effects of L-glutamate on astrocytes isolated from POA of neonatal male and female rats. The proliferation of astrocytes was measured by methods of cell count and cell cycle analysis. In addition, the activity of Ca(2+)/calmodulin-dependent protein kinase II (CaM kinase II) was assayed to understand its role in the glutamate-induced disturbance of the cell cycle progression of astrocytes. The results revealed that L-glutamate, at doses of 0.5 and 1.0 mM, inhibited the proliferation of astrocytes derived from male rats more severely than those derived from females. The L-glutamate treatment blocked the cell cycle progression and caused an accumulation of cells in the S phase. The activity of CaM kinase II declined more markedly in astrocytes derived from male rats than in those from females after glutamate treatment. These findings suggest that the proliferation of astrocytes derived from POA of neonatal rats can be inhibited in a sexually dimorphic manner by L-glutamate, possibly through blocking the cell cycle progression and partially related to the inactivation of the CaM kinase II.

Aging↗

Muscarinic receptors in preoptic area and hypothalamus: effects of cyclicity, sex and estrogen treatment.

Cholinergic muscarinic receptor binding was measured in the preoptic area (POA) and whole hypothalamus (HTH) of adult Sprague-Dawley rats using the tritiated antagonist quinuclidinyl benzilate ([3H]QNB) as the ligand. Binding of [3H]QNB expressed as fmol/mg protein was 30% higher in POA than in HTH from gonadectomized rats. Cyclic changes were observed in the POA with the highest binding at proestrus and the lowest binding at diestrus. In HTH, no significant changes occurred over the estrous cycle. Estrogen treatment (10 micrograms of estradiol benzoate (EB)/120 g b. wt./48 and 24 h before sacrifice) increased [3H]QNB binding by 42% in the POA and 17% in HTH, relative to the ovariectomized controls. The enhancement of [3H]QNB binding in POA as compared with controls was evident with both the filtration and the centrifugation methods, although binding levels were higher when centrifugation assay was used. A lower estrogen dose (2 micrograms EB/rat/48 and 24 h before sacrifice) which is routinely used to activate lordotic behavior in female rats increased muscarinic binding by 26% in the POA but had no appreciable effect in HTH. A significant sex difference was found in the ability of estrogen to induce [3H]QNB binding in the central nervous system (CNS). Estrogen was ineffective in altering [3H]QNB binding in either brain region of castrated males, although the level and pattern of cholinergic binding between untreated gonadectomized males and females were similar.2+ These data suggest that physiological changes in estrogen secretion over the estrous cycle are capable of modulating cholinergic muscarinic binding in the POA and these changes may be of physiological relevance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Restoration of bone mass in hpg mouse by preoptic area grafting.

Hereditary hypogonadism in the hpg mouse, caused by a deletion mutation in the gonadotropin-releasing hormone (GnRH) gene, is associated with sterility, absent ovarian development, and undetectable circulating sex steroids. Eight-month-old female hpg mice had a significantly reduced bone mineral density (BMD) at the lumbar spine, femur, and tibia. In addition, the mice showed significant reductions in liver and kidney weight, with virtually nonexistent ovaries. Successfully transplanted hpg mice with preoptic area grafts contained GnRH-positive neurons, consistent with our previous experience, and the host median eminence was innervated by GnRH immunoreactive fibers. A return of reproductive function was evident from increased ovarian weight and vaginal cornification. Of note was that grafted hpg mice showed a complete reversal to baseline of their BMD measured at all three sites. This establishes that the low bone mass that occurs in old hpg mice can be fully and rapidly ameliorated by preoptic area grafting.

Animals↗

Cholinergic activation of medial preoptic area by amygdala for ovulation in rat.

Ovulation blocked by amygdalar lesion was restored by carbachol injection into medial preoptic area (mPOA) in rats on the afternoon of proestrus. Both spontaneous and carbachol-induced ovulation was blocked by application of nicotinic and muscarinic cholinergic antagonists (mecamylamine and atropine) to mPOA. The effect was more pronounced in the latter case. The study suggests amygdalar facilitatory control of ovulation to be mediated via mPOA through the involvement of cholinergic mechanisms.

Amygdala↗

Sex-induced fos in the medial preoptic area: projections to the midbrain.

Sexual activity results in cells displaying Fos-like Immunoreactivity (FLI) in the medial preoptic area (MPOA) of male rats. This study combined retrograde tracing techniques with FLI to determine if MPOA cells displaying sex-induced FLI project to known efferent sites of the MPOA. FluoroGold was injected into the dorsal central gray, lateral central gray, ventral tegmental area, medial central tegmental field, or lateral central tegmental field of male rats that later engaged in sexual activity. Examination of FLI and FluoroGold in the MPOA revealed that the lateral region of the MPOA projected to the lateral central gray and contained smaller projections to the other regions. These findings suggest that the lateral MPOA contains secondary sex-relevant projections to the midbrain.

Animals↗

Sex difference in the neurotensin-immunoreactive cell populations of the preoptic area in quail (Coturnix japonica).

The distribution of neurotensin-immunoreactive cells and fibers was analyzed by immunocytochemistry in the forebrain of male and female Japanese quail (Coturnix japonica) by using an antibody directed against the C-terminal part of the molecule. Immunoreactive perikarya were located almost exclusively in the medial preoptic area with small populations also being present in the nucleus paraventricularis and in the tuberal region. Immunoreactive fibers were observed not only throughout the preoptic area-hypothalamus, but also in the septal region, nucleus intercollicularis, substantia grisea centralis and the classical catecholaminergic areas of the mesencephalon, such as the area ventralis of Tsai and the nucleus tegmenti pedunculo-pontinus, pars compacta. The preoptic neurotensin-immunoreactive cells were exclusively located within the boundaries of the sexually dimorphic medial preoptic nucleus. They were significantly more numerous in females than in males. In females, the number of neurotensin cells varied during the ovulatory cycle: fewer cells were observed in birds that were about to lay an egg (they had a calcified egg in the oviduct) than in those that had already laid or were not going to lay on that day. These data indicate major variations in the expression of neurotensin in response to neurochemical or neuroendocrine changes associated with ovulation.

Animals↗

Data on the absence of axon terminals of medial preoptic area neurons in the surface zone of the median eminence.

In order to investigate whether neurons of the medial preoptic area (MPOA) project to the surface zone (zona palisadica) of the median eminence (ME) and proximal part of the pituitary stalk, an electrolytic lesion or a frontal cut was placed in the pre- and suprachiasmatic region of the rat hypothalamus and the mentioned zone examined under the electron microscope. Degenerated nerve profiles were not observed int the zona palisadica following a lesion restricted to the MPOA or after a frontal cut at the posterior border of the MPOA. Altered elements were seen only in those cases in which the posterior part of the suprachiasmatic region was destroyed. The present data indicate that neurons of the MPOA do not terminate in the zona palisadica of the ME but presumably end on the nerve cells of the medial basal hypothalamus.

Animals↗

Estrogen binding macromolecules in hypothalamus-preoptic area of male and female gray short-tailed opossums (Monodelphis domestica).

Estrogen binding sites in the hypothalamus-preoptic area (HPOA) of adult male and female gray opossums (Monodelphis domestica) were characterized by incubating cytosols from gonadectomized animals with [3H]estradiol (E2) in the presence or absence of excess unlabeled E2. Scatchard analyses revealed that HPOA cytosols from both males and females contained high concentrations (25-30 fmol/mg protein) of binding sites with a very high affinity (Kd = 0.08-0.12 nM) for E2. There was no sex difference in either the number or the affinity of estrogen binding sites. Competition studies indicated that estrogen agonists and antagonists displaced [3H]E2 from binding sites in HPOA cytosols more effectively than did progestins, androgens, or adrenal corticoids. These data suggest that the HPOA of both male and female gray opossums contains macromolecules with several of the steroid binding properties characteristic of estrogen receptors.

Animals↗

Perfusion of the preoptic area with muscimol or prostaglandin E2 stimulates cardiovascular function in anesthetized rats.

The effect of unilateral perfusion of the preoptic area (POA) utilizing in vivo microdialysis with the GABAergic agonist, muscimol, or prostaglandin E2 (PGE2) on cardiovascular function (heart rate, blood pressure and cutaneous blood flow) was determined in halothane-anesthetized rats. Perfusion of muscimol or PGE2 increased the heart rate, 55 +/- 6 beats/min and 69 +/- 12 betas/min, respectively (P < 0.01). Cutaneous paw blood flow tended to decrease. Blood pressure did not change in response to the perfusion of muscimol, but increased 9 mmHg in response to the perfusion of PGE2 (P < 0.01). The increases in heart rate and blood pressure were blocked by systemic administration of propranolol or adrenalectomy (P < 0.01), suggesting that these effects were due to the activation of the sympathetic innervation of the heart or adrenal gland. It is proposed that the POA provides a tonic inhibitory afferent to posterior hypothalamus neurons which regulate cardiovascular function.

Adrenal Medulla↗

Sleep-inducing function of noradrenergic fibers in the medial preoptic area.

The aim of the investigation was to find out the role of noradrenergic (NE) terminals of the medial preoptic area (mPOA), in the regulation of sleep-wakefulness. Studies were conducted on free-moving adult male rats with chronically implanted cannulae in the mPOA. Sleep-wakefulness was assessed on the basis of EEG, EMG, and EOG recordings along with behavioral observations. Lesioning of catecholamine terminals (with 6-hydroxydopamine) in the mPOA produced an increase in quiet wakefulness. Prevention of NE fiber destruction, by pretreating the rats with imipramine, prevented this effect. This demonstrated that the increased quiet wakefulness produced by 6-OHDA was the result of NE fiber destruction. Changes in sleep-wakefulness were also assessed after microinjection of NE into the mPOA, in normal and ventral noradrenergic bundle (VNA)-lesioned rats. NE administration induced sleep in VNA-lesioned rats, and arousal in normal rats. The findings suggest that the NE terminals in the mPOA, projecting via VNA, play a role in the induction of sleep.

Animals↗

GABA augments basal and electrically stimulated 3H-norepinephrine release in hypothalamic, preoptic area and cortical slices of female rats.

These studies examined the regulation by GABA of norepinephrine release from hypothalamus, preoptic area and frontal cortex. Using superfused brain slices from female rats, we show that 100 microM GABA enhances both basal and electrically stimulated release of 3H-norepinephrine in all three brain regions. The GABAA agonist muscimol (100 microM) significantly augments 3H-norepinephrine release, but it is somewhat less effective than GABA. The GABAB agonist baclofen has little or no effect on basal 3H-norepinephrine efflux. GABA also augments both the magnitude and duration of electrically evoked 3H-norepinephrine release in slices from all three brain regions. GABA facilitation of electrically stimulated 3H-norepinephrine release is mediated through GABAA receptors as evidenced by its blockade by 10 microM bicuculline, a GABAA antagonist, but not by 200 microM 2-OH-saclofen, a GABAB antagonist. These data show that the inhibitory amino acid neurotransmitter GABA enhances both basal and evoked release of 3H-norepinephrine in brain slices from female rats. These effects are predominantly mediated by GABAA receptors. GABA modulation of hypothalamic norepinephrine release may play a role in the regulation of gonadotropin secretion and reproductive behaviors such as lordosis.

Animals↗

Neuronal circuitry in the basal septum and preoptic area of the rat.

Extracellular action potentials of spontaneously active units were studied in the basal septum and medial preoptic area (SPOA). Units responded in a similar way during stimulation of the amygdala, the reticular formation, the medial geniculate nucleus or the ventral hippocampus. The initial response was either short latency (6--35 msec) excitation or inhibition, the latter being predominant. A percentage of neurones (14.5%) did not respond. Only one response did not have an inhibitory component and responses have been further classified on the basis of the presence or absence of a postinhibitory excitation, and its rhythmicity. Single neurones tended to respond in a similar way to stimulation of different sites. Long inhibition (100--400 msec) is often preceded by excitation and may be a recurrent mechanism whilst short inhibition (18--55 msec) may be a 'direct' mechamism. Long inhibition may be mediated by GABA as it is weakened by intravenous bicuculline whilst short inhibition was not affected. A small amplitude barrage of action potentials at the onset of inhibition was suggested to be generated by inhibitory interneurones within the SPOA. Rhythmic postinhibitory excitatory responses suggest transmission of activity from stimulation sites to the SPOA via the thalamus. A hypothesis for local neuronal circuitry of spontaneously active neurones in the SPOA was proposed.

Amygdala↗

N-methyl-DL-aspartic acid lesions of the medial preoptic area disrupt ongoing parental behavior in male rats.

The effects of axon-sparing, neurotoxic lesions of the medial preoptic area (MPOA) with N-methyl-DL-aspartic acid (NMA) on previously established parental behavior in male rats were investigated. Adult, sexually-inexperienced male rats were gonadectomized and seven days later implanted sc with a single estradiol (E2)-filled Silastic capsule on treatment Day 1. Three progesterone (P4) capsules were implanted sc on treatment Day 3 and removed on Day 21, one day prior to the start of behavioral testing. Males were tested daily with foster pups in order to induce parental behavior, i.e., contacting the test pups, pup retrieval, grouping, and crouching over three foster pups. Full parental behavior appeared in these males after an average of 3 days. After testing on the third consecutive day of parental behavior, parental males were infused bilaterally with either NMA or vehicle into the MPOA. NMA infusions resulted in a significant decline in all components of parental behavior by the next test session, a deficit which persisted throughout the 5 days of post-infusion testing. In contrast, parental care continued to be displayed in animals given vehicle infusions. These findings demonstrate that the cells in the MPOA play an important role in regulating ongoing parental care in male rats and indicate that the neural substrates controlling parental behavior in male and female rats are similar.

Animals↗

Evidence for sexual differences in the preoptic area regulation of blood glucose in rats.

The effect of noradrenaline (NA) injection (20 or 40 nmol) into the preoptic area (POA) on plasma glucose and insulin was studied in male and female rats. The rats were implanted with chronic jugular catheters for blood sampling and unilateral intracerebral cannulas placed just above the POA. Blood samples were taken before and at 5, 10, 15, 30 and 60 min after NA injection. As early as 5 min after NA injection, plasma glucose levels rose rapidly in both male and female rats, reaching a peak at 15 min poststimulus. NA injection into the POA caused a dose-dependent hyperglycemic response in both male and female rats, although the response was more intense and longer lasting in females than in males. However, NA injection into the POA induced an increase in plasma insulin concentration in male but not in female rats. In addition, the increase in plasma glucose induced by 40 nmol NA injection in males preceded that of insulin. Plasma levels of glucose after POA injection of NA were already significantly elevated (p < 0.01) within the first experimental interval (5 min), whereas a plasma insulin increase were first detected 15 min post injection. We conclude that, when administered locally into the POA, NA can activate the sympathetic outflow expressed by a neurally mediated hyperglycemia which is more intense in females than in males. These data demonstrate that the POA has a sexually differentiated function in the regulation of glycemia.

Animals↗