Increase in sensitivity of the baroreceptor reflex following microinjection of carbachol into the posterior hypothalamic nucleus of awake rats.

In a rat model, the baroreceptor reflex can be assessed by graded infusions of either phenylephrine or sodium nitroprusside with continuous hemodynamic monitoring. Microinjection of the cholinergic agonist carbachol (CCh) into the posterior hypothalamic nucleus (PHN) evokes an increase in mean arterial pressure and a change in heart rate. Lower doses of CCh evoke only tachycardia, whereas middle and higher doses evoke a biphasic change in heart rate of tachycardia followed by bradycardia. The bradycardia following the microinjection of CCh into the PHN can be attenuated by the previous administration of the vasopressin V1 receptor antagonist [d(CH2 )5 Tyr(Me)] arginine vasopressin (AVPX). Circulating arginine vasopressin (AVP) has been shown to increase the sensitivity of the baroreceptor reflex by stimulating vasopressin V1 receptors in the area postrema. The attenuation by AVPX of the bradycardia that results following the high doses of CCh suggests that AVP is released into the circulation following stimulation of cholinergic systems within the PHN. Thus, microinjection of a high dose of CCh (11 nmol) into the PHN alters the sensitivity of the baroreceptor reflex by increasing peripheral levels of AVP.

Behavior and cellular evidence for propofol-induced hypnosis involving brain glycine receptors.

BACKGROUND: It is well documented that several general anesthetics, including propofol, potentiate glycine receptor function. Furthermore, glycine receptors exist throughout the central nervous system, including areas of the brain thought to be involved in sleep. However, the role of glycine receptors in anesthetic-induced hypnosis has not been determined. METHODS: Experiments were conducted in rats where the loss of righting reflex (LORR) was used as a marker of the hypnotic state. Propofol-induced LORR was examined in the presence and absence of strychnine (a glycine receptor antagonist), GABAzine (a gamma-aminobutyric acid A receptor antagonist), as well as ketamine (an antagonist of N-methyl-D-aspartic acid subtype of glutamate receptors). Furthermore, the effects of propofol on the currents elicited by glycine and gamma-aminobutyric acid were analyzed in neurons isolated from the posterior hypothalamus of rats. The effects of strychnine and GABAzine on propofol-induced currents were also evaluated. RESULTS: Strychnine and GABAzine dose-dependently reduced the percentage of rats exhibiting LORR induced by propofol. Furthermore, strychnine significantly increased the onset time and reduced the duration of LORR induced by propofol. In contrast, strychnine did not affect the LORR induced by ketamine. In addition, propofol markedly increased the currents elicited by glycine and GABA of hypothalamic neurons. Conversely, strychnine and GABAzine both profoundly attenuated the current induced by propofol. CONCLUSION: Strychnine, the glycine receptor antagonist, dose-dependently reduced propofol-induced LORR in rats and propofol-induced current of rat hypothalamic neurons. These results suggest that neuronal glycine receptors partially contribute to propofol-induced hypnosis.

Enhanced nitric oxide release/synthesis in the posterior hypothalamus during nitroglycerin tolerance in rats.

We have recently observed that increasing central noradrenergic transmission and sympathomimetic activity is involved with the complex hemodynamic effects during tolerance to nitroglycerin. The present study was to examine the release of nitric oxide (NO) in the posterior hypothalamus during tolerance to depressor responses to nitroglycerin and determine if, during the tolerance, endogenous NO synthesis is induced in the posterior hypothalamus. A microdialysis probe was implanted in the posterior hypothalamus and perfusion fluid was pumped through the probe at 2 microl/min in conscious rats. Tolerance to nitroglycerin was produced by three intravenous (i.v.) injections of 1.3 mg nitroglycerin each within 40 min compared to the same administrations of low dose of the drug, sodium nitroprusside and papaverine. Dialysate samples were collected 1 h before and 1 h each after injections for 8 h. Concentrations of nitrite (NO(2)(-)), nitrate (NO(3)(-)), and total nitrite plus nitrate (NO(x)(-)) were quantified in the samples by using chemiluminescence. The dose-response curve for arterial depressor induced by intravenous injection of the challenge doses of nitroglycerin was markedly shifted to the right at the first hour after nitroglycerin tolerance, lasted 3 to 5 h and reversed at 7 h. The dialysate NO(3)(-) and NO(x)(-) concentrations in the posterior hypothalamus were significantly increased at the first hour following nitroglycerin tolerance but were not altered by low dose of the drug, sodium nitroprusside, and papaverine. Nitroglycerin tolerance predominantly caused an increase in NO(3)(-) release in the posterior hypothalamus with no or small amount of changes in dialysate NO(2)(-) and the response was partially inhibited by pretreatment with N(G)-Propyl-L-arginine (NPLA) (1.0 mg/kg, i.p.), an inhibitor of neuronal NO synthesis. The increase of NO release in the posterior hypothalamus occurred at the first hour, lasted 2 to 3 h and reversed at 5 to 6 h during nitroglycerin tolerance. The results show that systemically administered high dose of nitroglycerin increases NO release in the posterior hypothalamus which matches the time interval of tolerance to arterial depressor response to the drug. Data suggest that there is an enhanced endogenous NO synthesis in the posterior hypothalamus which may affect central sympathetic functions during nitroglycerin tolerance.

Multiple hypothalamic sites control the frequency of hippocampal theta rhythm.

Stimulation of a neural pathway originating in the brainstem reticular formation, with synapses in the medial hypothalamus, activates the hippocampal theta rhythm. The frequency of reticular-elicited theta is determined in the medial supramammillary nucleus (mSuM) completely in anaesthetised rats, but only partially when the animal is awake. We tested other medial hypothalamic sites for their capacity to control theta frequency in awake rats. Blockade of sodium channels (1 microl fast infusion of the local anaesthetic procaine, experiment 1) or increased inhibition by GABA (Chlordiazepoxide [CDP], experiment 2) was found to reduce or increase the frequency of reticular-elicited theta, depending on the precise site of injection, in the region of the dorsomedial hypothalamic nucleus (DMH) and the posterior hypothalamic nucleus (PH). A band of null sites for CDP was located in the region of the ventral border of PH and dorsal border of mSuM. Using 0.5 and 1 microl CDP, and slow infusions (experiment 3), it was found that effective PH sites were also separate from mSuM in the rostrocaudal direction. In experiment 4, the DMH/PH region was mapped with unilateral and bilateral slow infusions of 0.5 microl CDP. CDP significantly reduced frequency in medial (periventricular) and dorsal PH, but not DMH. Bilateral injections appeared to generally sum the usual effects of unilateral injection, producing effects of intermediate size. However, the absolute frequency change in any given site, or with any pair of sites, did not exceed 1 Hz, which is similar to what is seen with single injections in mSuM. Overall, it appears that at, any one time, theta frequency may be determined by a complex interplay between distinct but interacting modulatory regions in the medial hypothalamus.

Inhibited hypothalamic histamine metabolism during isoflurane and sevoflurane anesthesia in rats.

BACKGROUND: Histamine is most densely distributed in the hypothalamus and has an important effect on consciousness or wakefulness. It has been little considered whether general anesthetics could exert their effects on hypothalamic histamine metabolism. The present study was conducted to investigate the effects of isoflurane and sevoflurane anesthesia on hypothalamic histamine metabolism. METHODS: Sixty male Wistar rats were divided equally into isoflurane and sevoflurane anesthesia groups. Each group was divided into three equal sub-groups: the control, anesthesia and recovery groups. The rats of the anesthesia and recovery groups were exposed to either 2% isoflurane or 3% sevoflurane for 30 min. The recovery group was kept in air for 30 min after anesthesia. The rats were decapitated to dissect out hypothalamus which was divided into the fore and rear portion. The contents of histamine and 1-methylhistamine, which is a main histamine metabolite, were determined by high-performance liquid chromatography. The obtained data were analyzed by one-way analysis of variance followed by Bonferoni's test. RESULTS: Histamine contents of the anterior and posterior hypothalamus in both isoflurane and sevoflurane groups increased significantly during the anesthesia and 1-methylhistamine contents of the anterior and posterior hypothalamus in sevoflurane group increased remarkably after anesthesia. The increases of histamine contents supposedly reflected inhibited histamine metabolism and the increases of 1-methylhistamine would be caused by acceleration of histamine degradation. CONCLUSIONS: Histamine metabolism was inhibited during both isoflurane and sevoflurane anesthesia and accelerated only in the posterior hypothalamus during the emergence from these anesthetics.

Estradiol acts locally within the retrochiasmatic area to inhibit pulsatile luteinizing-hormone release in the female sheep during anestrus.

In the present study we have identified a site of action of estradiol in the inhibition of LH secretion during anestrus in the ewe. In the first experiment, we studied six sites: the medial preoptic area, the lateral preoptic area, the ventromedial hypothalamus, the ventrolateral hypothalamus, the retrochiasmatic area (RCh), and the periventricular posterior hypothalamus. We compared the changes in parameters of pulsatile LH secretion (interpulse interval, mean nadir, mean amplitude, and mean area under curve) during three 6-h sampling periods: before and 30-36 h and 9 days after intracerebral implantation of crystalline estradiol. Animals that received estradiol in the RCh (n = 5) showed a significantly greater increase in both the intervals between pulses of LH (up 116%, p < 0.03) and the area under the curve (up 180%, p < 0.01) than any of the other groups of 7 animals. In the second experiment, implantation of estradiol in the RCh (n = 6) induced an increase in the intervals between pulses of LH (p < 0.03), whereas receiving an empty implant (n = 6) had no effect, showing that estradiol specifically induced increases in the intervals between pulses. Thus, estradiol appears to act in the RCh where the dopaminergic A15 nucleus, known to inhibit pulsatile LH release, is located.

Initiation of the oestradiol-induced inhibition of pulsatile LH secretion in ewes under long days: comparison of peripheral versus central treatment and neurochemical correlates.

In the ewe, the inhibition of pulsatile LH secretion by oestradiol during long days depends on dopaminergic activity and could involve amino acid transmitters. In the first experiment of the present study we observed the changes in LH secretion in ovariectomised ewes under long days immediately after subcutaneous implantation of oestradiol (peripheral treatment). In the second experiment, in order to identify the site of action of oestradiol, we observed the LH changes following intracerebral infusion of oestradiol through a microdialysis membrane (central treatment) within the preoptic area, the mediobasal hypothalamus (MBH) or the retrochiasmatic area (RCh) and measured amino acids and catecholaminergic transmitters and metabolites within the dialysates. With peripheral treatment, the amplitude, the nadir and the area under the LH pulse curve decreased within 4 to 8 h of the insertion of a subcutaneous oestradiol implant. After 18 h, the amplitude and the area under the pulses increased, as well as the intervals between pulses (from 49.9 + 1.4 min to 75.6 +/- 5.9 min). With central oestradiol treatment. LH changes were similar whatever the site of oestradiol infusion, suggesting either multiple sites of action or diffusion between structures. Twenty hours after the beginning of intracerebral oestradiol treatment, the amplitude and the area under the pulses increased, as did the interval between LH pulses (from 49.5 +/- 4.1 min to 73.2 +/- 14.2 min). Comparison of peripheral with central oestradiol treatment suggested that the long-lasting decrease in the nadir, as well as the transitory decrease in the amplitude and area, before 18 h in experiment 1 are reflections of hypophysial effects. In contrast, the increases in amplitude and area under the LH pulse curve seen 18-20 h after oestradiol in the two experiments could be due to the higher amplitude of LHRH pulses, as a result of an early stimulatory effect of oestradiol. After central oestradiol infusion, there was a decline in the concentration in the dialysate of two metabolites of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid in the RCh, suggesting an early inhibition of monoamine oxidase by the steroid. During the inhibition of LH pulsatility the concentration of gamma-aminobutyric acid in the dialysate from the RCh and the MBH increased, suggesting the participation of this transmitter in the changes induced by oestradiol under long days.

Lack of norepinephrine--neuropeptide Y interactions in the hypothalamic control of cardiovascular regulation in urethane-anesthetized rats.

Noradrenergic input to the hypothalamus is implicated in cardiovascular and behavioral regulation. The hypothalamus also contains high concentrations of neuropeptide Y (NPY), which often is colocalized in noradrenergic neurons. Systemically, NPY has been demonstrated to act synergistically with norepinephrine. Injections of concentrated solutions of NPY into the cerebral ventricles or hypothalamus have been found to alter ingestive behaviours, but the role of NPY in cardiovascular regulation is unknown. The objectives of this study were to determine if NPY injected directly into the hypothalamus elicits cardiovascular responses and (or) if the simultaneous administration of NPY with norepinephrine alters the cardiovascular responses elicited by norepinephrine alone. The hypothalamus of the urethane-anesthetized rat was mapped for heart rate and blood pressure responses to injections of one of the following: saline; NPY (1.9 or 0.6 pmol per injection site); norepinephrine (24, 81, or 243 nmol per injection site); or the combination of norepinephrine plus NPY. Site and drug selection were randomized. Injections of 0.25 microL were at 1.0 microL/min, bilaterally for bilateral structures and unilaterally for midline structures. Norepinephrine routinely elicited dose-dependent increases in blood pressure with latencies of approximately 1 min, which peaked by 3-5 min, accompanied or followed by tachycardia. Saline and NPY injections alone elicited no significant responses in any site. When NPY was injected together with norepinephrine, there were no significant alterations in cardiovascular variables except for attenuation of pressor responses when NPY was injected into the preoptic region and attenuation of tachycardia when NPY was injected into the caudal hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)

Augmented neuronal activity in the hypothalamus of spontaneously hypertensive rats.

Previous studies indicate a tonic GABAergic inhibitory mechanism in the posterior hypothalamus (PH) contributes to modulating cardiovascular activity. Blockade of GABA receptors on neurons in this area elicits an increase in sympathetic discharge, arterial pressure, and heart rate. It has been proposed that a deficit in this inhibitory system may be responsible for the elevated pressure in the spontaneously hypertensive rat (SHR). The purpose of this study was to determine if the spontaneous neuronal activity in the posterior hypothalamus of spontaneously hypertensive rats differs from that of age-matched normotensive Wistar-Kyoto rats (WKY). Single unit, extracellular recordings of posterior hypothalamic neurons were performed on both in vivo and in vitro preparations. The spontaneous firing rate of posterior hypothalamic neurons in the anesthetized adult SHR was significantly higher (3.66 +/- 0.55 Hz) compared to that of the anesthetized adult WKY rat (2.11 +/- 0.29 Hz). Moreover, more of the neurons in the anesthetized SHR (38%) had a bursting discharge pattern than in the WKY (16%). In order to exclude inputs from peripheral receptors or other brain areas, an in vitro preparation was used. Neurons from both young and adult SHRs also had an increased spontaneous discharge rate and higher percentage of burster-type cells in the posterior hypothalamus compared to neurons from age-matched WKYs in the brain slice preparation. Both the in vivo and in vitro findings support the possibility that an elevated neuronal activity in the posterior hypothalamus, a known pressor area, of the SHR contributes to the development and/or maintenance of hypertension in this animal model.

The responsiveness of D1- and D2-dopamine receptors in the striatum and hypothalamus of spontaneous and vasopressin hypertensive rats.

Low doses of apomorphine (20-50 micrograms/kg) induced an increase in the activity of an endogenous inhibitor of cAMP dependent protein Kinases (type I inhibitor) in the striatum, anterior and posterior hypothalamus of normotensive rats by stimulating D2-dopamine receptors. In contrast, high doses of the compound (2-10 mg/kg) produced a dose dependent decrease in type I inhibitor activity. In the posterior hypothalamus of vasopressin hypertensive rats and SHR the maximal increase of type I inhibitor activity was markedly higher than in normotensive animals. Moreover, apomorphine induced the increase of type I inhibitor activity in a much wider range of doses. Only as high dose of the compound as 10 mg/kg was able to decrease type I inhibitor activity. This points to a marked supersensitivity of D2 receptors and suggests the subsensitivity of D1 receptors in this brain area of hypertensive rats. In contrast, in the striatum and anterior hypothalamus of hypertensive rats the apomorphine dose response curves were similar to those in normotensive rats. Thus, it seems tha hypertension is associated with the alteration in sensitivity of D2 and D1 receptors in the posterior hypothalamus, the brain area involved in regulation of blood pressure.

Amphetamine affects the extinction of self-stimulation differently in prefrontal cortex and posterior hypothalamus of rats.

The effects of amphetamine on the extinction of intracranial self-stimulation (ICSS) and on postextinction ICSS performance were examined in rats implanted with electrodes either in medial prefrontal cortex (mPFC) or in the posterior hypothalamus-ventral tegmental area (PH-VTA). Lever-pressing for ICSS was allowed to stabilize in daily 15-minute sessions before each animal was exposed to 5 minutes of extinction (responding without reward). Animals were administered either 0.25 mg/kg d-amphetamine or saline before baseline, extinction and postextinction sessions. After amphetamine treatment, the number of lever presses during extinction was higher in mPFC animals and lower in PH-VTA animals compared with saline-treated controls. Rates did not change immediately after extinction but, one day later, rates had increased in all saline-treated animals (both PH-VTA and mPFC animals) and had decreased in all amphetamine-treated animals. These findings demonstrated that the effects of amphetamine on the extinction of ICSS were different in cortical and hypothalamic sites, possibly because of regional differences in stimulus-evoked reinforcement and inhibitory processes.

L-glutamate mapping of cardioreactive areas in the rat posterior hypothalamus.

The posterior hypothalamus has long been regarded as a CNS region that provides a sympatho-excitatory influence on the cardiovascular system and functions in thermoregulation as a heat-producing center. These ideas have been based on data derived from electrical stimulation and lesion experiments. These methods are now regarded as inadequate for accurate localization of CNS functions. In order to re-examine the function of the posterior hypothalamus, a chemical stimulation study was performed. Microinjections of the excitatory amino acid L-glutamate were made in the posterior hypothalamus of pentobarbital-anesthetized rats. This method was used in combination with autoradiography to localize [3H]glutamate, which was included with the injectate. No pressor responses were elicited from any site within the posterior hypothalamus. In contrast, chemical stimulation of the posterior periventricular hypothalamus produced large decreases in blood pressure (delta BP = 25 mm Hg) and in heart rate (delta HR = 30 bpm). Injections in the posterior hypothalamic nucleus elicited small reductions in blood pressure and heart rate. Injections in the dorsal hypothalamic area produced a similar small response. Injections ventral to the periventricular zone were also weakly reactive, but a significant elevation in rectal temperature was seen. To summarize, the most cardioresponsive area was within the periventricular zone caudal to the posterior hypothalamic nucleus and was situated near the fasciculus retroflexus.

Effects of a major androgen-dependent urinary protein, alpha 2u-globulin on the pituitary-gonadal axis and hypothalamic monoamines in adult male mice.

The purpose of the present study was to evaluate the effects of alpha-2u-globulin, a sex-dependent male rat urinary protein on pituitary-gonadal functions and hypothalamic monoamine contents in male mice. Adult male mice, maintained under standardized laboratory conditions (L:D, 14:10) were injected subcutaneously with alpha-2u-globulin at a dose of 1 mg/animal/day or with vehicle daily for 14 days and killed 16 h after the last injection. Plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T) and testicular levels of T were measured by radioimmunoassays. The concentrations of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) in medial basal hypothalamus (MBH) and anterior hypothalamus (AH) were measured by high performance liquid chromatography. Administration of alpha-2u-globulin led to a significant increase in plasma FSH and LH levels (P less than 0.05) as well as in plasma and testicular T levels (P less than 0.025). In the MBH of alpha-2u-globulin treated mice, there were significant elevations of NE (P less than 0.025), DA (P less than 0.01) and 5-HT (P less than 0.025) contents. In the AH, both DA (P less than 0.025) and 5-HT (P less than 0.01) contents were decreased while NE content remained unaltered. These results indicate that administration of alpha-2u-globulin can lead to a significant stimulation of pituitary-testicular axis and that this effect may be mediated through alteration of hypothalamic monoamines.

Injection of muscimol into posterior hypothalamus blocks stress-induced tachycardia.

We have previously shown that the physiological and behavioral manifestations of emotional stress are produced when drugs impairing gamma-aminobutyric acid (GABA)-mediated synaptic inhibition are injected into the posterior hypothalamic nucleus in rats [Wible, J.H., Jr., F.C. Luft, and J.A. DiMicco. Am. J. Physiol. 254 (Regulatory Integrative Comp. Physiol. 23): R680-R687, 1988]. The purpose of this study was to assess further the potential role of GABA receptors in this region in the response to stress using muscimol, a GABAA receptor agonist. In six chronically instrumented conscious rats, air stress after vehicle treatment evoked marked and sustained tachycardia (+130 +/- 14 beats/min at +10 min) accompanied by a less dramatic increase in arterial pressure (+14 +/- 3 mmHg). Microinjection of muscimol (10 ng; 88 pmol) at the same posterior hypothalamic site in which GABA blockade causes cardiovascular changes similar to those seen in stress produced a modest depression of cardiovascular function in unstressed animals (-28 +/- 5 beats/min and -6 +/- 3 mmHg). However, similar treatment with muscimol virtually abolished the stress-induced tachycardia in the same rats (+9 +/- 8 beats/min), while having no significant effect on baroreflex-evoked increases in heart rate caused by intravenous infusion of sodium nitroprusside (4 micrograms). These findings support a role for activation of neurons in the posterior nucleus of the hypothalamus in the generation of stress-induced cardiovascular changes and for control of this mechanism by local GABA receptors.

A critical role of the posterior hypothalamus in the mechanisms of wakefulness determined by microinjection of muscimol in freely moving cats.

In order to determine critical sites within the hypothalamus responsible for the induction and maintenance of wakefulness (W), we performed microinjections of muscimol, a potent gamma-aminobutyric acid (GABA) agonist, in various lateral hypothalamic regions of freely moving cats. We found that bilateral injections of a small amount of muscimol (0.1-1.0 micrograms/0.5 microliters) in the preoptic and anterior hypothalamus and rostral mesencephalic tegmentum resulted in increased vigilance and insomnia. In contrast, microinjections of muscimol in the middle and anterior parts of the posterior hypothalamus induced long-lasting behavioral and electroencephalographic signs of sleep with short latency. The hypersomnia was characterized by a significant increase in both light and deep slow wave sleep (SWS), and a nearly complete suppression of paradoxical sleep (PS). Animals with muscimol microinjections in the ventrolateral part of the posterior hypothalamus, however, exhibited increased SWS followed by a significant increase in PS. When injected into the posterior hypothalamus of insomniac cats pretreated with p-chlorophenylalanine (PCPA), muscimol induced not only SWS but also PS with short latency. The present data thus support the hypotheses that the posterior hypothalamus plays a critical role in the mechanisms of W and that sleep might result from functional blockade of the hypothalamic waking center.

[The destruction of perikaryas of the mesencephalic reticular formation and the posterior hypothalamus does not cause major disorders of awakening in the cat]. / La destruction des périkaryas de la formation réticulée mésencéphalique et de l'hypothalamus postérieur n'entraîne pas de troubles majeurs de l'éveil chez le chat.

Ibotenic acid microinjections have been realized at the level of the mesencephalic reticular formation and the posterior hypothalamus in 7 cats. This technique has led to a quasi-total destruction of cell bodies in the two areas (including the histaminergic neurons). 2 to 3 days after such lesions, there were no major effects on behavioral waking. These results do not favor the hypothesis of the existence of a waking system at the level of the mesencephalic reticular formation and/or posterior hypothalamus.

Long-lasting insomnia induced by preoptic neuron lesions and its transient reversal by muscimol injection into the posterior hypothalamus in the cat.

In order to analyse the role of the anterior hypothalamus in the regulation of the sleep-waking cycle we made bilateral neuronal lesions at different levels of the anterior hypothalamus in cats, by means of microinjections of a cell-specific neurotoxin:ibotenic acid. These lesions resulted in severe insomnia in eight cats. This insomnia was characterized by a large decrease or even disappearance of paradoxical sleep and deep slow wave sleep and, to a lesser extent, by a decrease of light slow wave sleep, for 2-3 weeks. In the other five animals, we observed a large reduction of deep slow wave sleep (0-40% of control level), but a less intensive decrease of time spent in paradoxical sleep (50-75% of control level) and no marked effect on light slow wave sleep. During the first 3-6 postoperative days we also noticed hyperthermia in all cats; thereafter, the animals presented only a slight increase in brain temperature which did not appear to trigger the sleep impairment. Histological analysis of the different lesions revealed that the insomnia could be attributed to neuronal cell body destruction in the mediobasal part of the anterior hypothalamus covering; the medial preoptic area and a narrow portion of the lateral preoptic area as well as a restricted part of the anterior hypothalamic nucleus. In order to investigate the putative role of the posterior hypothalamic structures in the mechanism of insomnia after lesion of the mediobasal preoptic area neurons we injected an agonist of GABA into the ventrolateral part of the posterior hypothalamus to locally depress the neuronal activity. The bilateral intracerebral microinjection of muscimol (0.5-5 micrograms) induced a transient intensive hypersomnia (slow wave sleep and paradoxical sleep). These findings indicate that neuronal cell loss in the mediobasal preoptic area induced a long lasting insomnia. Thus, it may be hypothesized that the integrity of this structure is necessary for sleep appearance. Finally, our data are in keeping with an intrahypothalamic regulation of the sleep-waking cycle.

Stimulation of H fields of Forel decreases total lung resistance in dogs.

Although there is considerable evidence that the H fields of Forel of the posterior diencephalon play an important role in the regulation of cardiovascular function, little is known about the role these areas play in the control of airway caliber. In chloralose-anesthetized paralyzed dogs, we used both electrical and chemical means to stimulate the H fields of Forel, while we monitored breath-by-breath changes in total lung resistance (TLR), a functional index of airway caliber. Electrical stimulation (200-250 microA, 80 Hz, 0.75 ms) of 82 histologically confirmed sites significantly decreased TLR from 9.2 +/- 0.4 to 7.9 +/- 0.4 cmH2O.l-1.s (P less than 0.01). The bronchodilation evoked by electrical stimulation was unaffected by beta-adrenergic blockade with propranolol but was abolished by cholinergic blockade with atropine. The increases in airway caliber evoked by stimulation were often accompanied by increases in phrenic nerve activity. Chemical stimulation of 21 of 82 sites with microinjections of DL-homocysteic acid (83 nl, 0.2 and 0.5 M), which stimulates cell bodies but not fibers of passage, also decreased TLR from 8.3 +/- 0.5 to 7.3 +/- 0.5 cmH2O.l-1.s (P less than 0.03). We conclude that stimulation of cell bodies in the H fields of Forel produces bronchodilation by withdrawal of cholinergic tone to airway smooth muscle.

Blood pressure increases after injection of neuropeptide Y into posterior hypothalamic nucleus.

Unilateral microinjection of neuropeptide Y (NPY; 0.235-2.35 nmol) into the posterior hypothalamic nucleus was found to evoke a concentration-dependent increase in mean arterial pressure (MAP) of Urethane-anesthetized rats. Concentration-dependent pressor responses were also elicited by unilateral administration of histamine (0.543-17.9 nmol) into the posterior hypothalamic nucleus. Administration of 30 nmol of the histamine H1-receptor antagonist, chlorpheniramine, but not 43.5 nmol of the histamine H2-receptor antagonist, cimetidine, into the posterior hypothalamic nucleus 10 min before 5.43 nmol histamine administration, significantly attenuated the histamine-induced pressor response. These concentrations of chlorpheniramine or cimetidine did not affect the increase in MAP, which could be evoked by the administration of 5.48 nmol of the cholinergic muscarinic agonist carbachol into the posterior hypothalamic nucleus. The carbachol-induced increase in MAP was, however, completely blocked by administration of 12 nmol of the cholinergic muscarinic antagonist atropine into the posterior hypothalamic nucleus 10 min before carbachol administration. This concentration of atropine did not affect the histamine-induced pressor response. Administration of atropine or chlorpheniramine into the posterior hypothalamic nucleus 10 min before 2.35 nmol NPY significantly attenuated the pressor response evoked by NPY. Cimetidine, on the other hand, was unable to significantly affect the increase in MAP evoked by NPY. These results demonstrate that NPY administered into the posterior hypothalamic nucleus can elicit a pressor response, and that this pressor response might involve local histaminergic and cholinergic neuronal pathways.