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Effects of adrenalectomy, propranolol and methylatropine on the increase in heart rate induced by injection of dermorphin in the rat anterior hypothalamic nucleus.

Anterior hypothalamic injections of 40 pmol dermorphin, a potent opiate receptor agonist, increased heart rate 17% and had no effect on blood pressure in halothane-anesthetized rats. Administration of the beta-receptor antagonist, propranolol, during the peak response to dermorphin, reduced the heart rate to levels not different from pretreatment control; pretreatment with propranolol completely blocked the tachycardia produced by a subsequent injection of dermorphin. In contrast, neither adrenalectomy nor pretreatment with methylatropine altered the response to dermorphin. These data suggest that increased activity of the sympathetic nervous system, primarily to the heart, and not increased release of adrenal catecholamines or inhibition of parasympathetic nervous system activity, is responsible for the increase in heart rate resulting from injection of dermorphin into the anterior hypothalamic nucleus.

Adrenalectomy↗

Distribution of neurons in the anterior hypothalamic nucleus activated by blood pressure changes in the rat.

Electrophysiological and Fos-like protein immunocytochemical methods were used to identify the number and distribution of anterior hypothalamic neurons that are activated by changes in arterial pressure. First, in anesthetized, male Sprague-Dawley rats, arterial pressure increases and decreases led to differential activation of neurons in the anterior hypothalamic nucleus. Most of the units that responded to a rise in arterial pressure with a decrease in activity (pressor units) were located in the central part of the anterior hypothalamic nucleus, whereas units that increased firing when arterial pressure rose (the depressor units) were found throughout the nucleus. Second, in awake, male Sprague-Dawley rats, Fos-like protein immunoreactivity was mapped following sustained arterial pressure changes. Within the anterior hypothalamus, reduction in arterial pressure increased the number of Fos-labeled neurons primarily in the paraventricular nucleus and to a lesser extent in the anterior half of the anterior hypothalamic nucleus. In contrast, elevation in arterial pressure increased Fos labeling throughout the anterior hypothalamic nucleus and to a lesser extent in the paraventricular nucleus.

Animals↗

The organum vasculosum of the lamina terminalis regulates noradrenaline release in the anterior hypothalamic nucleus.

Changes in either plasma sodium concentration or arterial pressure can differentially affect hypothalamic neurons. For instance, increases in plasma NaCl concentration decrease noradrenaline release from nerve terminals in the anterior hypothalamic nucleus, while increases in arterial pressure unrelated to an elevation in plasma NaCl enhance noradrenaline release in anterior hypothalamic nucleus. The present study tests the hypothesis that in the rat the organum vasculosum of the lamina terminalis (an osmosensitive area of the brain) detects rises in plasma NaCl concentration and conveys this information to anterior hypothalamic nucleus. The axons projecting from the organum vasculosum of the lamina terminalis to the hypothalamus were unilaterally cut immediately caudal to organum vasculosum of the lamina terminalis, and five days later, 3-methoxy-4-hydroxy phenylglycol (the major metabolite of noradrenaline in brain) was continuously monitored in the ipsilateral or contralateral anterior hypothalamic nucleus in response to an intravenous infusion of hypertonic saline. In spontaneously hypertensive rats, the infusion decreased the 3-methoxy-4-hydroxy phenylglycol concentration by 24+/-2% in the anterior hypothalamic nucleus contralateral to the lesion, and in control spontaneously hypertensive rats. In contrast, in the anterior hypothalamic nucleus ipsilateral to the lesion, hypertonic saline infusion caused a 58+/-3% increase in 3-methoxy-4-hydroxy phenylglycol. These data support the hypothesis that the organum vasculosum of the lamina terminalis is part of the circuit that transmits information concerning plasma NaCl concentration to anterior hypothalamic nucleus.

Animals↗

Alpha2A-adrenergic receptors mediate sympathoinhibitory responses to atrial natriuretic peptide in the mouse anterior hypothalamic nucleus.

In the rat, activation of alpha2-adrenergic receptors in the anterior hypothalamic nucleus inhibits sympathetic nervous system activity. Furthermore, local release of atrial natriuretic peptide inhibits norepinephrine release in this nucleus, blocking local activation of alpha2-adrenergic receptors, and thereby contributes to NaCl-sensitive hypertension in spontaneously hypertensive rats. To further test the specificity of this mechanism, either alpha2-adrenergic receptor agonists or atrial natriuretic peptide was microinjected into anterior hypothalamic nucleus of conscious C57BL/6 mice in which the alpha2-adrenergic receptor was functionally deleted by a single point mutation (n=10 per group). In control mice, microinjection of either clonidine or guanabenz (10-3 to 10-7 mol/L) caused a rapid fall in mean arterial pressure that lasted for several minutes. In the knockout mice there was no response to the injection of either dose of either agonist. Microinjection of atrial natriuretic peptide (10-6 to 10-7 mol/L) caused a rapid increase in mean arterial pressure (8.2+/-1.3 and 6.55+/-1.2 mm Hg, respectively) in the control mice that was similar to the responses previously observed in Wistar-Kyoto rats. In contrast, the microinjections did not significantly alter mean arterial pressure in the knockout mice. These experiments demonstrate that in the anterior hypothalamic nucleus of the mouse (and probably in the rat) alpha2A-adrenergic receptors mediate both sympathoinhibitory responses to alpha2-adrenergic receptor agonists and the action of atrial natriuretic peptide.

Adrenergic alpha-2 Receptor Agonists↗

Organization of projections from the anterior hypothalamic nucleus: a Phaseolus vulgaris-leucoagglutinin study in the rat.

Anterior hypothalamic nucleus (AHN) projections were examined with the Phaseolus vulgaris-leucoagglutinin (PHA-L) method in adult male rats. Labeled axons from the AHN follow three major routes. 1) A large ascending pathway ends densely in the telencephalon, particularly in the lateral septal nucleus. Axons along this route provide moderate to dense input to the medial and lateral preoptic areas, and a few are also observed in the septofimbrial nucleus and fimbria; the latter end in the temporal hippocampus. A few axons reach the amygdala through the bed nuclei of the stria terminalis, which receive a moderate input, and then the stria terminalis, and others reach it by way of the ansa peduncularis. 2) The second pathway travels dorsal to the AHN, ending densely in rostral perifornical regions of the lateral hypothalamic area, and the rostral ventrolateral tip of the nucleus reuniens. The parataenial and rostral paraventricular thalamic nuclei also receive a significant input. Some fibers and boutons were also observed in the rhomboid, interanterodorsal, and mediodorsal nuclei, and others course through the stria medullaris to the lateral habenula. 3) the largest pathway descends through dorsal and ventral routes in the medial hypothalamic zone before ending massively in the periaqueductal gray. Dorsal route fibers provide inputs to the zona incerta and posterior hypothalamic nucleus, whereas more ventral axons generate dense terminal fields in the ventromedial nucleus capsule and core, and dorsal premammillary nucleus. The retrochiasmatic area, dorsomedial nucleus, and medial supramammillary nucleus also receive significant inputs, and a few axons end in the subparafascicular nucleus, superior colliculus, and mammillary body. The caudalmost axons were seen in the pontine central gray and reticular formation. These pathways are bilateral, usually with a distinct ipsilateral predominance. The overall pattern of efferents from anterior, central, and posterior parts of the AHN is similar, whereas the relative densities of particular terminal fields may vary considerably. Projections from adjacent parts of the retrochiasmatic and perifornical areas are also described. The results are discussed in terms of neural circuitry that may be involved in mediating interactions between animals.

Animals↗

Efferent connections of the anterior hypothalamic nucleus: a biocytin study in the cat.

The efferent connections of the anterior hypothalamic nucleus (AH) were examined using biocytin as anterograde tracer in the cat. The results provide several new findings in addition to confirming earlier observations. In the hypothalamus, the AH projections terminated mainly in the medial regions which are related to the defensive, reproductive and feeding behaviors, and autonomic functions. Moreover, we found dense patches of the AH terminals in the medial preoptic area and ventromedial hypothalamic nucleus, which suggests the existence of modular connections between sub-regions of each nucleus. In addition, the AH projected to regions which may be related to the emotional and autonomic responses, i.e., such regions in the amygdala, midline thalamus, septum, subthalamus, and midbrain. The data suggest that the AH may play an important role in the autonomic functions and behaviors between animals, and thus may play a key role in the defensive behavior elicited in the medial preoptic area and ventromedial hypothalamic nucleus.

Animals↗

Circadian rhythms of adenosine triphosphate contents in the suprachiasmatic nucleus, anterior hypothalamic area and caudate putamen of the rat--negative correlation with electrical activity.

Contents of adenosine triphosphate (ATP) in the suprachiasmatic nucleus (SCN), anterior hypothalamic area (AH) and caudate putamen (CPu) were determined every 4 h in rats kept under constant dark conditions. All tested regions of the brain exhibited circadian rhythms in ATP content. Among these, the amplitude of the rhythm was largest in the SCN. Peaks of the ATP content were observed at circadian time 18 in the SCN, 6 in the AH and 10 in the CPu. In view of the observation that at around these peak times electrical or glucose uptake activity of each brain region was lowest, the present result suggests that ATP content is negatively correlated with electrical or glucose uptake activity.

Adenosine Triphosphate↗

Evidence for the existence of an enkephalin-containing pathway from the area just ventrolateral to the anterior hypothalamic nucleus to the lateral septal area of the rat.

The afferent source of enkephalin-like immunoreactive (ELI) fibers in the lateral septal area of the rat was elucidated experimentally by means of an indirect immunofluorescence technique. These ELI fibers had almost completely disappeared on the operated side after the destruction of the area just ventrolateral to the anterior hypothalamic nucleus, where a number of ELI cells was detected. This fact strongly suggests that these ELI cells project ipsilaterally to the lateral septal area.

Afferent Pathways↗

Serotonergic terminals in the anterior hypothalamic nucleus involved in the prolactin release during suckling.

The present studies were designed to localize within the hypothalamus and neighboring areas the serotonergic terminals which are implicated in suckling-induced PRL release. The initial experiments were performed to characterize the circulating hormone profile induced by suckling in lactating rats, previously separated from their pups. Five minutes of suckling induced an increase in serum PRL only. During these 5 min, 5-hydroxytryptamine (5-HT) and 5-hydroxyindole-3-acetic acid concentrations were determined in the pars nervosa of the pituitary gland, hypothalamic nuclei, dorsal, and median raphe nuclei. An increase by 80% (P less than 0.01) in 5-HT concentration was found only in the rostral part of the anterior hypothalamic nucleus (rNHA). In order to investigate causal effect between the altered 5-HT neuronal activity in the rNHA and the suckling-induced PRL release, serotonergic neurotoxin was bilaterally injected in the rNHA on day 1 of lactation. Litters were adjusted to eight pups each and weighed daily to determine litter growth rates. On day 8 of lactation, litters were separated from their mothers for 4 h and allowed to suckle for 5 or 15 min after which the mothers were decapitated. Litters from lesioned animals grew at a lower rate (P less than 0.0001) than control and sham-operated animals. Serum PRL increased with suckling in animals bearing the correct rNHA lesions, but the values were lower than in control and sham-operated animals after 5 (P less than 0.05) and 15 (P less than 0.01) min. Therefore we postulate that the rNHA is the site of termination of a stimulatory serotonergic pathway on PRL release induced by suckling.

5,7-Dihydroxytryptamine↗

Intrahypothalamic 5,7-dihydroxytryptamine: temporal analysis of effects on 5-hydroxytryptamine content in brain nuclei and on facilitated lordosis behavior.

The long-term relationship between serotonin (5-HT) levels in discrete hypothalamic nuclei and female rat sexual behavior, the lordosis response, was examined following intrahypothalamic injection of 5,7-dihydroxytryptamine (5,7-DHT). One week following 5,7-DHT injection, 5-HT levels in the ventromedial hypothalamic nucleus, dorsomedial nucleus, anterior hypothalamic nucleus and the medial preoptic nucleus were approximately 90% depleted as compared to sham animals. Other hypothalamic and preoptic areas including the arcuate-median eminence, vertical nucleus of diagonal band and lateral septal nucleus showed smaller reductions in 5-HT, from 40 to 70% of sham values. At this time estrogen-dependent lordosis behavior in the lesioned group was facilitated. Behavioral facilitation was greatest at 4 weeks post lesion when depletion of 5-HT in the VMN was maximal. 5-HT levels increased at 57 days after 5,7-DHT treatment in most areas, and by 71 days post lesion, no significant differences in 5-HT levels were found between sham and 5,7-DHT-treated groups. Concomitant with the increases in 5-HT, facilitated lordosis behavior gradually decreased. Loss of behavioral facilitation appeared to be most closely related to increases in content of 5-HT in the ventromedial nucleus. These results further support the hypothesis that 5-HT endings in the hypothalamus exert tonic inhibitory regulation over hormone-dependent lordosis in the female rat. They also indicate that regenerating 5-HT fibers in the hypothalamus can reinstate a normal pattern of hormone-dependent behavioral function.

5,7-Dihydroxytryptamine↗

In situ hybridization study of interleukin-1 beta mRNA induced by kainic acid in the rat brain.

The distribution patterns of interleukin-1 beta (IL-1 beta) mRNA in various brain regions of saline- and kainic acid-treated rats were examined using in situ hybridization technique. In normal rat brain, the signals of IL-1 beta mRNA were observed in the cerebellar Purkinje cells and in dispersed cells in the hypothalamus. In the case of the kainic acid treatment, IL-1 beta mRNA was intensely induced in the olfactory bulb, lateral septum, thalamus, hypothalamus, polymorphic layers of hippocampus, piriform cortex, amygdala, entorhinal cortex and cerebral cortex at 2 h after the injection of kainic acid. In the hypothalamic region, we observed the induction of IL-1 beta mRNA around the paraventricular hypothalamic nucleus, anterior hypothalamic area, dorsomedial and ventromedial hypothalamic nucleus, mammillary regions and arcuate nucleus. The signal of IL-1 beta mRNA was still expressed 4 h after treatment with kainic acid, less intensely than at 2 h, but above the control level. In these regions, IL-1 beta mRNA was expressed mainly in the glial cells, which were densely stained by Cresyl violet and did not contain glial fibrillary acidic protein. These results suggest that IL-1 beta is produced by a certain type of glial cells, maybe microglia, and might have regulatory functions in the central nervous system.

Animals↗

Afferent and efferent connections of the medial preoptic area in the rat: a WGA-HRP study.

Afferent and efferent connections of the medial preoptic area including medial preoptic nucleus (MP) and periventricular area at the MP level were examined using WGA-HRP as a marker. Injections were performed by insertion of micropipette containing (1) small amount of HRP powder or (2) dryed HRP solution for 24 to 48 hr until the fixation or for 5 min respectively. Dorsal and ventral approaches of injection micropipettes were performed and the results were compared. Previously reported reciprocal connections with lateral septum, bed nucleus of the stria terminalis, medial amygdaloid nucleus, lateral hypothalamic nucleus, paraventricular hypothalamic nucleus, ventromedial hypothalamic nucleus, arcuate nucleus, supramammillary nucleus, central gray at the mesencephalon, raphe dorsalis, raphe medianus, and lateral parabrachial nucleus have been confirmed. In addition, we found reciprocal connections with septo-hypothalamic nucleus, amygdalo-hipocampal nucleus, subiculum, parafascicular thalamic nucleus, posterior thalamic nucleus at the caudo-ventral subdivision, median preoptic nucleus, lateral preoptic nucleus, anterior hypothalamic nucleus, periventricular area at the caudal hypothalamic level, dorsomedial hypothalamic nucleus, posterior hypothalamic nucleus, dorsal and ventral premammillary nucleus, lateral mammillary nucleus, peripeduncular nucleus, periventricular gray, ventral tegmental area, interpeduncular nucleus, nucleus raphe pontis, nucleus raphe magnus, pedunculo-pontine tegmental nucleus, gigantocellular reticular nucleus and solitary tract nucleus. The areas which had only efferent connections from MP were accumbens, caudate putamen, ventral pallidum, substantia innominata, lateral habenular nucleus, paratenial thalamic nucleus, paraventricular thalamic nucleus, mediodorsal thalamic nucleus, reuniens thalamic nucleus, median eminence, medial mammillary nucleus, subthalamic nucleus, pars compacta of substantia nigra, oculomotor nucleus, red nucleus, laterodorsal tegmental nucleus, reticular tegmental nucleus, cuneiform nucleus, nucleus locus coeruleus, and dorsal motor nucleus of vagus among which substantia innominata and median eminence were previously reported. Efferent connections to the nucleus of Darkschewitsch, interstitial nucleus of Cajal, dorsal tegmental nucleus, ventral tegmental nucleus, vestibular nuclei, nucleus raphe obsculus were very weak or abscent in the ventral approach while they were observed in dorsal approach. Previously reported afferent connections from dorsal tegmental nucleus, cuneiform nucleus, and nucleus locus ceruleus were not detected in this study.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Oxytocin in microdissected hypothalamic nuclei. Significant differences between prepubertal and sexually mature female rats.

We measured the concentration of oxytocin and vasopressin in microdissected areas of the hypothalamus and posterior pituitary in weanling and adult female rats. Oxytocin concentration was significantly less in adult rats as compared to weanling rats in the supraoptic nucleus, median eminence, and retrochiasmatic area with no significant differences in vasopressin content. This may indicate differences in hypothalamic-neurohypophyseal pathways in adult and weanling rats. There was a significantly greater concentration of oxytocin in the adult rat in the paraventricular nucleus, suprachiasmatic nucleus, anterior hypothalamic nucleus, and posterior pituitary, again with no significant difference in vasopressin concentration. Our results are consistent with a role for sexual maturation in increasing synthesis of oxytocin in specific hypothalamic nuclei resulting in increased storage of oxytocin in the posterior pituitary.

Animals↗

Distribution of immunoreactive melanin-concentrating hormone in the central nervous system of the rat.

The distribution of melanin-concentrating hormone-like immunoreactivity (MCH-LI) in 41 microdissected brain and spinal cord regions was determined using radioimmunoassay with antibodies to salmon MCH. The highest concentration of MCH-LI was detected just ventral to the zona incerta (subzona incerta) (2923.2 fmol/mg protein). Very high concentrations of MCH-LI (greater than 1000 fmol/mg protein) were detected also in the nucleus of the diagonal band, medial forebrain bundle, posterior hypothalamic nucleus and medial mammillary nucleus. High concentrations of the peptide (between 500-1000 fmol/mg protein) were measured in 11 brain regions, including bed nucleus of stria terminalis, paraventricular nucleus, anterior hypothalamic nucleus, median eminence, parabrachial nucleus. Moderate concentrations of MCH-LI (between 250-500 fmol/mg protein) were measured in 16 brain regions, such as frontal cortex, central amygdaloid nucleus, medial septum, periventricular nucleus (preoptic) and nucleus of the solitary tract. Low concentrations of MCH-LI (less than 250 fmol/mg protein) were measured in 9 brain regions such as cortical areas, hippocampus, caudate nucleus and substantia nigra. Cervical spinal cord and neurointermediate lobe of the pituitary gland contain low concentrations of the peptide.

Animals↗

Aromatization and 5alpha-reduction of androgens in discrete hypothalamic and limbic regions of the male and female rat.

The in vitro aromatization and 5alpha-reduction of androgens to estrogens and dihydrotestosterone (DHT) were determined in incubations of microdissected brain regions of male and female gonadectomized, adrenalectomized rats. Metabolites formed from [1alpha,2alpha-3H]androstenedione or [1alpha,2alpha-3H]testosterone were purified by celite liquid-liquid partition chromatography, silica gel chromatography and recrystallization to stable 3H/14C ratios. The medial preoptic nucleus-anterior hypothalamic nucleus exhibited the highest aromatase activity and the second highest conversion to DHT. The lateral preoptic and lateral hypothalamic nuclei showed little aromatase activity yet exhibited high rates of formation of DHT. The medial basal hypothalamus showed the second highest level of aromatase activity but consistently formed the lowest amount of DHT. The discrect anatomical localization of these enzymatic conversions is suggestive of their being involved in the physiological actions of androgens.

Amygdala↗

Regional distribution of luteinizing hormone-releasing hormone (LH-RH) in rat brain determined by microdissection and radioimmunoassay.

We have re-examined the distribution of LH-RH in rat brain and in particular those rostral hypothalamic areas reported to contain perikarya by immunocytological techniques. Adult male rats were decapitated and 20 discrete brain structures micro-dissected. Tissue from single rats was homogenized in 50 microliter 0.1 N HCl and 40 microliters of this acid extract was radioimmunoassayed for LH-RH using the R-42 antibody. Low but detectable concentrations which ranged from0.2 to 1.0 pg/micrograms protein were found in the interstitial nucleus of the stria terminalis (ventral aspect), medial preoptic nucleus (dorsal and ventral aspects), lateral preoptic nucleus, anterior hypothalamic nucleus, paraventricular nucleus, ventromedial nucleus (medial and lateral aspects) and the dorsomedial nucleus. Slightly higher concentrations (1.0--4.0 pg/micrograms protein) were measured in a rostral, medial basal corridor made up of the suprachiasmatic preoptic nucleus, the suprachiasmatic nucleus and the retrochiasmatic area. LH-RH was not detected (i.e. less than 0.8 pg/area) in the bed nucleus of the diagonal band of Broca, caudate nucleus, lateral septal nucleus or the cingulate cortex.

Animals↗

Localization of cells retaining 3H-estradiol in the forebrain of rabbits.

Ovariectomized rabbits received 3H-estradiol via an ear vein and were killed one hour later. Autoradiograms were prepared and exposed up to six months. Labeled cells, as indicated by many silver grains over the nucleus of a neuron, were found in many nuclei of the brain. Thus, the bed nucleus of the stria terminalis had labeled cell bodies. The stria terminalis leads into the medial preoptic area where great numbers of cells concentrated the estrogen. Farther into the hypothalamus the labeled cells were numerous in the ventromedial and arcurate nuclei. Other locations with labeled cells were the lateral septal nucleus and nucleus accumbens septi, the periventricular preoptic nucleus, anterior hypothalamic nucleus, nucleus supraopticus diffusus, posterior hypothalamic nucleus, and premammillary nucleus. The labeled cells could be followed into the central gray surrounding the aqueduct of Sylvius. The amygdaloid nuclei, and in particular the medial amygdaloid nucleus, had labeled cells as did the most ventral posterior part of the hippocampal cortex. The results are discussed in comparison with those in the rat, and with reference to physiologic data.

Amygdala↗