Effects of electrical stimulation in the lower brainstem on temperature regulation in the unanaesthetized guinea-pig

Summary Electrical stimulation in lower brainstem areas presumed to be parts of the ascending noradrenergic system was carried out in the unanaesthetized guinea-pig. In the same animals noradrenaline (NA) was also injected into the anterior hypothalamus. Certain points in the lower brainstem were found, the stimulation of which resulted in a rise of oxygen uptake (more than 60% over the resting level), of body temperature and of electrical muscle activity at an ambient temperature of 29–30°C. Respiratory rate also rose on stimulation, while heart rate did not show a consistent change. All these changes were found to be very similar to those obtained after an intrahypothalamic injection of NA. When the electrical stimulations at the same sites were repeated several times the extent of rise in oxygen uptake became gradually smaller, amounting to only half of the initial response after four periods of stimulation. An intrahypothalamic injection of NA restored the effectiveness of electrical stimulation in the lower brainstem to the original extent.These results suggest that the thermogenesis evoked by the electrical stimulation of these lower brainstem areas may be ascribed to the activation of ascending noradrenergic pathways terminating in the hypothalamus.This study was supported by the Deutsche Forschungsgemeinschaft (SFB 122, Projekt B1).     

Vascular endothelial growth factor-B is neuroprotective in an in vivo rat model of Parkinson's disease

Occlusal disharmony induced by placing an acryl cap on the lower incisors of rats is perceived as chronic stress. This chronic stress activates corticotropin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN), resulting in stimulation of the hypothalamic-pituitary-adrenal (HPA) axis. The ventral ascending noradrenergic bundles (V-NAB) from the brainstem innervate the PVN. To investigate the relationship between the response of the HPA axis and the V-NAB, we examined changes in extracellular noradrenaline (NA) in the PVN and plasma corticosterone, the final output of the HPA axis, following occlusal disharmony in rats injected with 6-hydroxydopamine (6-OHDA), a specific catecholamine neurotoxin. 6-OHDA microinjection into the V-NAB reduced the magnitude of the responses of extracellular NA in the PVN and the plasma corticosterone to occlusal disharmony. Our results suggest that V-NAB to the PVN are involved in occlusal disharmony-induced activation of the HPA axis.     

Electrically evoked noradrenaline release in the rat hypothalamic paraventricular nucleus studied by in vivo electrochemistry: characterization and facilitation by increasing the stimulation frequency

The hypothalamic paraventricular nucleus is densely innervated by noradrenergic terminals mainly originating in the A1 group within the ventrolateral medulla. An oxidation signal corresponding to extracellular catechols was recorded from the paraventricular nucleus of urethane anaesthetized rats every 1 s by differential pulse amperometry at + 105 mV combined with carbon fiber electrodes. In basal conditions, both extracellular noradrenaline and DOPAC, which are synthesized by noradrenergic terminals, contributed to this oxidation signal. Electrical stimulations of the rostral part of the A1 group were applied for 10 or 20 s every 10 min at physiological frequency (3-20 Hz). They induced an immediate increase in the oxidation signal which lasted as long as the stimulation. This increase was due to the evoked noradrenaline release since it was enhanced by pargyline, desipramine and amphetamine and it was attenuated by alpha-methyl-p-tyrosine and reserpine. The amplitude of the evoked noradrenaline release depended non-linearly on the frequency of the stimulation (from 3 to 20 Hz). When expressed per pulse, noradrenaline release was facilitated four-fold as the frequency increased from 3 to 20 Hz. Central noradrenergic neurons exhibit a tonic activity in a single spike discharge pattern with a mean frequency below 5 Hz but they respond to physiological stimuli by short bursts of action potentials at 20 Hz. Therefore, the present data show that noradrenergic terminals convert physiological impulse flow into noradrenaline release as a high pass filter which enhances the signal-to-noise ratio in response to phasic stimuli.     

Pattern of drinking and feeding produced by hypothalamic norepinephrine injection in the satiated rat.

Injection of norepinephrine into the perifornical region of the anterior hypothalamus elicited both drinking and feeding in satiated rats. Analysis of these behaviors revealed the following: (1) Both responses were dose-dependent, occurring at doses at least as low as 0.5 mug. (2) The drinking response (1-4 ml) had a latency of around 1.5 min and a duration of 2-3 min. It was followed within a minute or two by eating (2-4 g) that lasted approximately 20 min. It was also followed by a period of drinking suppression that lasted approximately 60 min. (3) Satiation from the ingestion process appeared to be a primary factor in terminating the elicited feeding response, whereas a time-related factor was important in terminating the elicited drinking. (4) These ingestive responses produced by noradrenergic stimulation of the anterior perifornical hypothalamus were found to bear striking similarities to the rat's natural feeding behavior and premeal component of his natural food-associated drinking behavior. (5) These noradrenergically elicited responses could not be observed with lateral hypothalamic stimulation, while only feeding was elicited by ventromedial hypothalamic stimulation. (6) The drinking induced by central noradrenergic stimulation, in contrast to that induced by peripheral beta-adrenergic stimulation, was unaffected by nephrectomy.     

Bradycardia evoked by hypothalamic stimulation in the rabbit: Dependence upon the arterial blood pressure

The spinal cord was transected in adult New Zealand White rabbits anaesthetized with urethane plus chloralose. The level of transection was in the mid-cervical region. The animals were then ventilated mechanically and the arterial blood pressure was maintained with an intravenous infusion of noradrenaline solution. Stimulation of the hypothalamus 1–2 mm lateral to the third ventricle and 1.5–3 mm dorsal to the mammillary nuclei, in a region known to evoke pressor responses and bradycardia in normal anaesthetized rabbits, never evoked pressor responses in the spinally transected rabbits. Bradycardia was evoked only when the mean arterial blood pressure was maintained above 44–49 mmHg. At higher pressures stimulation evoked a greater bradycardia and the relationship between bradycardia and pressure was approximately linear over much of the range of pressures tested (up to 116 mmHg).Because the threshold mean arterial blood pressure at which hypothalamic stimulation evoked bradycardia was similar to the threshold pressures reported in the literature for baroreceptor activation in the rabbit and because the curve of bradycardia:pressure was similar to published curves of baroreceptor and baroreflex activity against blood pressure, it is concluded that the bradycardia evoked by hypothalamic stimulation in the rabbit is mediated by a neural pathway in the hypothalamus that can increase the gain of the cardio-inhibitory baroreceptor reflex.     

Influence of noradrenergic input into the hypothalamic paraventricular nucleus on fever in the guinea-pig

The febrile response of guinea-pigs to a bacterial pyrogen was tested under different experimental conditions: (1) during electrical stimulation of the hypothalamic paraventricular nucleus (PVN), (2) after destruction of noradrenergic afferents into the PVN by 6-hydroxydopamine (6-OHDA), (3) during a microinfusion of noradrenaline (NA) into the PVN. Electrical stimulation of the PVN neurons by implanted microelectrodes reduced the febrile response to 45% of the control values. This confirmed the proposed antipyretic function of these neurons. Chronic destruction of noradrenergic afferents to the PVN by microinjected 6-OHDA also resulted in a significant reduction of febrile responses to 38% of the control values. A microinfusion of NA into the PVN enhanced the febrile responses to bacterial endotoxin by 39% in comparison to animals microinfused with the solvent (0.9% NaCl). Immunoreactivity to an antiserum against arginine vasopressin (AVP) was compared in PVN neurons of 6-OHDA-treated and of control animals. The number of AVP-immunoreactive perikarya and the intensity of immunoreactivity were increased in the animals treated with 6-OHDA, especially in the medial part of the PVN. Since fever was increased by microinfused NA and decreased by 6-OHDA treatment, we assume an inhibitory influence of noradrenergic brain stem afferents on the proposed antipyretic vasopressinergic system of the PVN.     

Peripheral and intrahypothalamic cholecystokinin act on the noradrenergic “feeding circuit” in the rat's diencephalon

To determine whether the food satiating action of cholecystokinin (CCK) involves the noradrenergic ‘feeding circuit’ in the hypothalamus, two studies were undertaken with the unrestrained rat. In the first set of experiments, microinjection cannulae were stereotaxically implanted to rest within sites in the hypothalamus where norepinephrine microinjected in a dose of 2.5 μg, in 0.75 μl caused the satiated rat to eat food mash. CCK-octapeptide injected intraperitoneally in doses of 0.5–1.0 μg/kg immediately prior to the intrahypothalamic injection of norepinephrine significantly suppressed this norepinephrine-induced feeding. At several microinjection sites in the dorsal hypothalamus and pre-optic area, the direct infusion of 75 or 150 ng CCK just prior to a norepinephrine injection likewise attenuated the catecholamine-induced eating.In the second study, 2.0 μCi [¹⁴C]norepinephrine was infused into the hypothalamus through pushpull guide cannulae positioned at loci known to release endogenous norepinephrine, in order to radiolabel cellular stores of the amine. During a sequence of perfusions, the labelled tissue was perfused with an artificial cerebrospinal fluid, at 25 μl/min, by means of push-pull cannulae. 1.0 μg/kg CCK given intraperitoneally unexpectedly evoked the relase of [¹⁴C]norepinephrine at circumscribed medial and rostral hypothalamic sites implicated in the control of feeding. Analysis of push-pull perfusates by high performance liquid chromatography verified that endogenous norepinephrine was released.These results suggest that endogenous CCK interacts functionally with a pathway of noradrenergic neurons responsible for initiating satiety, or with those neurons that activate a feeding response.     

Differential effects of ascending neurons containing dopamine and noradrenaline in the control of spontaneous activity and of evoked responses in the rat prefrontal cortex

The medial prefrontal cortex receives converging projections from the mediodorsal thalamic nucleus, dopaminergic cells from the ventral tegmental area dn noradrenergic cells from the locus coeruleus. Stimulation of the ventral tegmental area inhibits the spontaneous activity of prefrontal cortical neurons and blocks the excitatory response evoked by stimulation of the mediodorsal thalamic nucleus (10 Hz). The aim of the present study was to compare the influence of dopaminergic and noradrenergic afferents on the spontaneous and evoked activity of medial prefrontal cortical neurons. In ketamine-anaesthetized rats, repetitive stimulation (20 Hz, 10 s) of the locus coeruleus produced a long-lasting post-stimulus inhibition (mean duration: 45 s) of the spontaneous activity of 56% of the tested cells. This effect was decreased markedly following selective destruction of the ascending noradrenergic pathways (local 6-hydroxy-dopamine injection) or depletion of cortical catecholamines by alpha-methyl-para-tyrosine pretreatment, suggesting that these inhibitory responses are mediated by noradrenergic neurons. The excitatory response to mediodorsal thalamus nucleus stimulation (10 Hz) could still be evoked during the post-stimulus inhibitory period induced by locus coeruleus stimulation (20 Hz, 10 s) resulting in the enhancement of signal-to-noise ratio. On the other hand, a population of prefrontal cortex neurons (26%) was found to be reproducibly activated by noxious tail pinch. This evoked response was still present during the post-stimulus inhibitory period induced by locus coeruleus stimulation but was completely suppressed during stimulation of the ventral tegmental area (10 Hz). In conclusion, these results indicate that the dopaminergic and noradrenergic systems exert a completely distinct control of information transfer in the medial prefrontal cortex.     

Excitatory amino acid receptors in the periaqueductal gray mediate the cardiovascular response evoked by activation of dorsomedial hypothalamic neurons

Neurons in the region of dorsomedial hypothalamus are involved in the organization of the physiological responses to emotional stress. We have recently shown that the cardiovascular response evoked by activation of dorsomedial hypothalamus neurons is largely dependent on a synaptic relay with the lateral/dorsolateral periaqueductal gray region. In this study, we aimed to investigate whether excitatory amino acid receptors at the lateral/dorsolateral periaqueductal gray region are involved in mediating the response evoked by activation of dorsomedial hypothalamus neurons. In conscious rats, the cardiovascular effects produced by microinjection of GABA(A) receptor antagonist, bicuculline methiodide into the dorsomedial hypothalamus were evaluated before and after injection of different excitatory amino acid antagonists into lateral/dorsolateral periaqueductal gray region. Pretreatment of lateral/dorsolateral periaqueductal gray region with the non-selective ionotropic excitatory amino acid receptor antagonist kynurenic acid or with the N-methyl-D-aspartate receptor-selective antagonist, MK-801, largely reduced the tachycardic and pressor effects evoked by activation of dorsomedial hypothalamus neurons by bicuculline methiodide microinjection (heart rate 90 and 74%; blood pressure 81 and 84%, respectively). The non-N-methyl-D-aspartate receptor-selective antagonist 6-cyano-7-nitroquinoxaline-2,3-dione, did not alter the cardiovascular response evoked by dorsomedial hypothalamus activation. In an additional series of experiments, microinjection of the N-methyl-D-aspartate receptor agonist, N-methyl-D-aspartate, into the lateral/dorsolateral periaqueductal gray region, evoked an increase in heart rate and a pressor response that was accompanied by an increase in locomotor activity. These effects were not altered by pretreatment of lateral/dorsolateral periaqueductal gray region neurons with 6-cyano-7-nitroquinoxaline-2,3-dione but were completely abolished by MK-801. Altogether, these findings indicate that the cardiovascular response evoked by dorsomedial hypothalamus activation involves a synaptic relay at the lateral/dorsolateral periaqueductal gray region that is mediated at least in large part by excitatory amino acid receptors, possibly N-methyl-D-aspartate receptors.     

The effects of lesions of lateral tegmental noradrenergic neurons on components of sexual behaviour and pseudopregnancy in female rats

Lesions (electrolytic and neurotoxic, using 6-hydroxydopamine) have been made of the projections of medullary noradrenergic neurons in the ascending ventral noradrenergic pathway in female rats. The lesions caused major depletion of noradrenaline in sub-cortical structures, notably the hypothalamus. In behavioural tests, these lesions selectively impaired sexual receptivity, measured as lordosis responses, but did not abolish proceptivity (soliciting). The impaired behaviour is critically dependent on somatosensory stimulation generated by the male during a mount. So, too, is pseudopregnancy since stimulation of the uterine cervix during coitus is essential for the prolongation of luteal life which underlies it. The ability to induce a pseudopregnant state was also abolished by the same ventral noradrenergic pathway lesion.These data, together with supportive evidence from experiments using procaine anaesthesia, have led us to suggest an important function of subcortically projecting noradrenergic neurons in the central transmission and/or processing of somatosensory information in neuroendocrine systems. We also present data suggesting that the effects of noradrenergic neuron activity are dependent on dopaminergic mechanisms more directly concerned with the control of motivated behaviour and anterior pituitary function.     

Differential cardiovascular changes as a function of stimulation electrode site in rabbit hypothalamus

Twenty chronically prepared, unanesthetized rabbits received both high-frequency (200 pulse/sec), short pulse-train (1.0 sec) and relatively low-frequency (25 pulse-sec), long pulse-train (10 sec) electrical stimulation of the hypothalamus. High-frequency, short pulse-train stimulation elicited a pressor response and bradycardia at all 27 electrode sites. In contrast, three other cardiovascular response patterns were obtained following low-frequency, long pulse-train stimulation. These latter patterns reflected a medial-lateral organization of autonomic function within the hypothalamus. Whereas all 15 lateral hypothalamic placements yielded depressor responses, 7 of 12 medial hypothalamic placements yielded pressor responses and tachycardia. Cardiovascular changes following administration of selective autonomic blocking agents (e.g., phentolamine, propranolol, methylatropine) suggest that high-frequency, short pulse-train stimulation elicited a pressor response followed by a reflexive bradycardia essentially mediated by an increase in vagal restraint. In contrast, the heart rate changes observed to low-frequency, long pulse-train stimulation all appear to have been importantly influenced by changes at the heart in beta-adrenergic activity.     

Release and modulation of release of serotonin in rabbit superior colliculus

The release of previously incorporated [3H]serotonin and its presynaptic modulation were studied in slices of rabbit superior colliculus. Electrical stimulation at frequencies of 0.017-3 Hz greatly increased the outflow of tritiated compounds; this response was almost abolished by tetrodotoxin and in a low calcium medium. Unlabelled serotonin, when added in the presence of nitroquipazine, an inhibitor of high-affinity neuronal serotonin uptake, reduced the electrically evoked overflow of tritium, an effect antagonized by metitepin. Given alone, metitepin caused an increase. The evoked overflow was also decreased by clonidine, and the effect of clonidine was counteracted by phentolamine. Phentolamine itself increased the overflow response. However, this was probably not due to antagonism against an inhibitory effect of endogenous noradrenaline because, first, the selective alpha 2-adrenoceptor antagonist idazoxan did not share with phentolamine the overflow-enhancing effect, second, phentolamine continued to increase the overflow after noradrenergic axons had been destroyed by 6-hydroxydopamine, and third, the facilitatory effects of metitepin and phentolamine were not additive. Phentolamine, like metitepin, antagonized the presynaptic inhibitory effect of serotonin, indicating that it may increase the evoked overflow of tritium by blocking serotonin receptors rather than alpha-adrenoceptors. Ethylketocyclazocine decrease the electrically evoked overflow, and its effect was prevented by naloxone: peptides selective for opioid mu- or delta-receptors caused no change. Nicotine increased the basal outflow of tritium (in the absence of electrical stimulation); the increase was attenuated by hexamethonium and low calcium medium. No or minimal changes in tritium outflow were obtained with beta-adrenoceptor, dopamine receptor, muscarine receptor and GABA receptor ligands or with substance P and glutamate. In conjunction with our previous studies, these results indicate that serotonin is a neurotransmitter in the superior colliculus. Its release is modulated through presynaptic autoreceptors (probably 5-HT1), alpha 2-adrenoceptors, opioid kappa-receptors and nicotine receptors, of which only the autoreceptors receive an endogenous input, at least under the experimental conditions chosen. Each of the three groups of collicular monoamine axons that we have studied recently (cholinergic, noradrenergic, serotoninergic) possesses a specific pattern of presynaptic, release-modulating receptors. A physiological role seems likely only for the alpha 2-autoreceptors at the noradrenergic and the 5-HT1-autoreceptors at the serotoninergic axons.     

Changes in body weight and food-related behaviour induced by destruction of the ventral or dorsal noradrenergic bundle in the rat

Three experiments contrasted the effects of 6-hydroxydopamine-induced lesions of the ventral noradrenergic and dorsal noradrenergic projections, predominantly to hypothalamus and cortex, respectively, upon body weight changes and food-related behaviour in the rat. In general, ventral noradrenergic bundle lesions enhanced weight gain and these effects were exaggerated by the provision of palatable cheese to the standard chow diet. In contrast, lesions of the dorsal noradrenergic bundle produced minor changes in body weight. Associated with the effects of ventral noradrenergic bundle lesions were hyperphagia, enhanced suppression of intake of food adulterated with quinine, (at high concentration), a small attenuation of food neophobia, and enhanced acquisition, but not performance, of the eating response to tail-pinch stimulation. These ventral noradrenergic bundle lesions failed to alter basal activity levels, amphetamine anorexia or the diurnal pattern of eating or activity. In contrast, lesions of the dorsal noradrenergic bundle did not produce either hyperphagia or enhanced rejection of food adulterated with quinine. However, there was a strong attenuation of food neophobia and a retarded acquisition (but unimpaired performance) of eating in response to tail-pinch stimulation.

The results are discussed in connection with previous studies of ventral and dorsal noradrenergic bundle lesions, with the effects of ventromedial hypothalamic lesions and with the underlying behavioural and physiological processes that mediate these contrasting effects of different neuroanatomical patterns of central noradrenaline depletion.     

Effects of mesencephalic central gray and raphe nuclei lesions on hypothalamically induced escape

Central gray (CG) lesions, in particular those located in its anterior part, provoked in about half of the lesioned rats a decrease in switch-off responses (SOR) induced by medial hypothalamic stimulation. Such a decrease in performance, followed by a partial or even total recovery, occurred only when the stimulation site was located in the postero-medial part of the medial hypothalamus. Occurrence and duration of the decrease in SOR did not depend on a possible severance of noradrenergic fibers that ascend from the locus coeruleus and course along the CG, since bilateral destruction of the locus coeruleus did not alter SOR. On the other hand, a lasting facilitation of SOR was observed in those rats in which the CG lesion extended more caudalle fully explained by an interruption of serotonergic fibers ascending from the raphé nuclei since lesions limited to the dorsal nucleus as well as combined lesions of the dorsal and medial raphé nuclei induced only a transient facilitation, whereas a lasting one was provoked both by raphé lesions that encroached upon the ventro-medial tegmentum and by CG lesions that only partially destroyed the dorsal raphé nucleus.     

The involvement of noradrenergic ascending pathways in the stress-induced activation of ACTH and corticosterone secretions is dependent on the nature of stressors

Summary The aim of the present study was to explore in male rats the role of the catecholaminergic innervation of the hypothalamus in corticotropic and adrenal responses to different kinds of stress conditions. For this purpose, 6-hydroxydopamine (3 g in 0.2 l saline) was stereotaxically and bilaterally infused at two levels of the main noradrenergic ascending brain stem bundle (NAB-X). The efficiency of catecholaminergic denervation of the hypothalamus was checked by measuring noradrenaline concentrations in paraventricular nuclei punches by HPLC and was confirmed by a 86% fall in noradrenaline levels of NAB-X rats killed after the stress experiments. Seven days after lesioning the NAB, sham operated controls and NAB-X lesioned animals were divided into 4 groups and submitted to 4 different stressors, i.e.: 2 min ether vapors (n = 5), 1 h immobilization (n = 7), i.v. histamine (2 mg/kg; n = 7) or i.v. insuline (10 I.U./kg; n = 8) injections. ACTH and corticosterone were measured in blood samples sequentially taken from a chronic carotid cannula, before stress and at short intervals over the 2 following hours. In comparison to the respective control groups, NAB-X dramatically reduced the ACTH response to ether (-78%) and to restraint (-53%) stress whereas the corticosterone response was affected to a lesser extent. In contrast, NAB-X slightly altered these responses in the histamine-treated group, although, surprisingly, the ACTH response tended to decrease and that of corticosterone to increase. Finally, NAB-X provoked a biphasic response to insulineinduced hypoglycemia, with a very early (5 min) rise in ACTH and corticosterone in comparison to the control group, followed by a trend to low hormonal levels up to 120 min. These results strongly suggest a differential involvement of the hypothalamic noradrenergic innervation upon the hypothalamic-pituitary-adrenal axis according to the nature of stress conditions.     

A microinjection study of the control of antidiuretic hormone release by the supraoptic nucleus of the hypothalamus in the cat

1. The release of antidiuretic hormone (ADH) has been studied in the chloralose anaesthetized cat after microinjection of various agents directly into the brain, in particular the supraoptic nucleus of the hypothalamus (SON). The concentration of ADH in jugular venous blood was determined using the waterloaded, alcohol anaesthetized rat assay. The position of the microinjection cannula was located post mortem in stained brain sections.2. Nicotine, noradrenaline (NA) and hypertonic saline caused release of ADH, whereas microinjections of isotonic saline did not affect the blood level of the hormone.3. Nicotine administered to other sites in the central nervous system (C.N.S.) could also cause ADH release. Hypertonic saline proved to be an ineffective stimulus at all the tested sites outside the supraoptic region.4. The ganglion-blocking agents hexamethonium and pempidine inhibited the releasing action of nicotine at the SON in most of the experiments. These blocking drugs had no effect on osmotic release. When administered alone, both hexamethonium and pempidine had variable, but analogous effects on the hormone output.5. The alpha-adrenoreceptor blocking drug, phentolamine, stimulated ADH release, but the beta-receptor blocking drug, propranolol, had no such effect. Both drugs appeared to have inhibitory action on noradrenergic release of ADH, but neither had a consistent effect on the osmotic release of the hormone.     

Divergent action of verapamil perfused in two hypothalamic areas on body temperature of the cat

Guide cannulae for push-pull perfusion were bilaterally implanted stereotaxically within the anterior hypothalamic, preoptic area (AH/POA) and posterior hypothalamus (PH) of the cat. Catecholamine-reactive sites were identified within AH/POA in which a microinjection of norepinephrine (NE) (5.0 micrograms) evoked a characteristic, transient hypothermia. Similarly the cation-reactive region within the PH was identified in which excess Ca2+ (25 mM) also evoked a hypothermic response. When verapamil was perfused at a rate of 25.0 microliters/min in a concentration of 0.4 or 2.0 micrograms/microliter within AH/POA at a NE-sensitive site, a concentration-dependent decline in the core temperature of the cat occurred. Conversely, verapamil perfused in the same manner with a Ca2+-reactive site caused an intense rise in the cat's body temperature which also was concentration dependent. These results show that the localized blockade of slow Ca2+ channels exerts direct, differential physiological effects within central nervous system tissue. In this case, verapamil mimics noradrenergic effects within the AH/POA; however, the hyperthermic response following Ca2+ channel blockade within tissue of the PH resembled that produced by ethyleneglycoltetraacetic acid or Na ions.     

Hypothalamic receptors influencing the secretion of corticotrophin releasing hormone in the rat

1. The production of corticotrophin releasing hormone (CRH) by the rat hypothalamus in vitro was studied in the presence and absence of various neurotransmitter substances and drugs which mimic or antagonize their actions.2. Acetylcholine, nicotine and bethanechol increased, in a dose-related manner, hypothalamic CRH release and content but the maximal responses to bethanechol or nicotine were less than those to acetylcholine.3. The actions of acetylcholine were antagonized by atropine, pempidine and hexamethonium but were completely inhibited only when atropine and pempidine were given together. The effects of nicotine were abolished by pempidine but not by atropine while those of bethanechol were abolished by atropine but not by pempidine.4. Acetylcholine-induced hypothalamic CRH activity was also antagonized by cyproheptadine but not by methysergide.5. 5-Hydroxytryptamine caused dose-related increases in hypothalamic CRH release and content. Its effects were antagonized by cyproheptadine and methysergide but not by atropine, pempidine or hexamethonium.6. Acetylcholine-induced increases in hypothalamic CRH production were reduced by GABA, noradrenaline, adrenaline, methoxamine and phenylephrine but not by isoprenaline. The actions of GABA were antagonized by bicuculline and those of noradrenaline by phentolamine but not by atenolol.7. The results suggest the presence of nicotinic and muscarinic cholinoceptors, 5-hydroxytryptamine receptors, alpha-adrenoceptors and GABA-receptors within the hypothalamus all of which may be important in the control of CRH secretion.     

Hypothalamic modulation of baroreceptor afferent unit activity.

Unit responses to sinus nerve stimulation were recorded in the medulla. A conditioning stimulus to the posterior hypothalamus produced inhibition of 65% of unit responses to sinus nerve stimulation as early as 7 ms and extending as long as 790 ms after conditioning; 50% recovered after 300 ms. Unit responses to hypothalamic stimulation alone were also recorded in the medulla, some in the same loci as other unit responses to sinus nerve stimulation. They could be activated by contralateral as well as ipsilateral hypothalmic stimulation and showed recurrent bursts of firing over a 1,000-ms poststimulus interval. Evoked potentials and unit responses were recorded in the posterior hypothalamus, some occurring within 10--20 ms poststimulation of the sinus nerve, indicating that baroreceptor information is ascending in a time sufficiently short to involve the hypothalamus in reflex regulation of blood pressure as well as more generalized homeostatic responses which include the cardiovascular system.     

Individual differences in temporal lobe sensory processing of threatening stimuli in the cat.

In Experiment I, neurosensory responses from three limbic areas in the cat brain were recorded when cats of differing defensive temperamental traits were exposed to species characteristic threat. The cats investigated were more or less defensive in response to rats and conspecific threat howls. The behavioral disposition of these cats was stable over retest periods of more than one year. It was found that during visual inspection of rats, more defensive cats displayed greater neural activity in the amygdala and the ventromedial hypothalamus than less defensive cats, who showed no change over baseline. Neurosensory response of the amygdala to conspecific threat howls was also found to be greater in more defensive cats. In contrast, there was no neural response to threat howls in the hypothalamus. Neurosensory response to mice was different from the response to rats and threat howls. Visual inspection of the mouse was associated with a decrease in activity in the amygdalas of more defensive cats. Finally, response of the ventral hippocampus was unspecific, appearing to signal only a change in the stimulus environment. The increase in hypothalamic neural activity in response to rats in more defensive cats appeared to be driven by a potentiated output from the amygdala, since the ratio of hypothalamic to amygdala neurosensory response to rats was greater than one in more defensive cats, but equal to one in less defensive cats. Output of the amygdala was directly investigated using evoked potential techniques in Experiment II. Potentials evoked in the hypothalamus by amygdala stimulation were larger in more defensive cats. Size of the hypothalamic potential was highly correlated with the ratio of hypothalamic to amygdala neurosensory response (ratio response) to rats. Removing the effects of size of the hypothalamic evoked potential from the ratio response by analysis of covariance eliminated the difference between more and less defensive cats in ratio response to rats. The significance of these findings for the physiological bases of defensive response to threat and of temperamental traits are discussed.