Epinephrine-independent production of hyperuricemia by means of hypothalamic stimulation in the conscious rat

The electrical stimulation of the ventromedial hypothalamus with 0.6 mA current produced an acute hyperuricemia associated with a rise in plasma allantoin in the conscious rat. Adrenal demedullation did not depress the hyperuricemic response. Even after the demedullation, neither propranolol nor phentolamine had any significant effects as well. These results indicate that endogeneous catecholamines are not involved in the production of the hyperuricemia; this is in sharp contrast with our previous result demonstrating the development of hyperuricemia via adrenal epinephrine by stimulating the ventromedial nucleus with 0.2 mA current. It is concluded therefore that ventromedial hypothalamic stimulation is capable of producing two different types of hyperuricemia, i.e. adrenal-epinephrine-dependent and epinephrine-independent, by varying the intensity of the stimulation current.     

The ventromedial nucleus of the hypothalamus and the hormonal arousal of sexual behaviors in the female rat

Bilateral lesions of the ventromedial nucleus of the hypothalamus interfered with the estrogenic induction of sexual receptivity in the female rat, but seemingly did not affect the ability of female rats to show lordosis following combined stimulation with estrogen and progesterone. In addition, ventromedial hypothalamic lesions did not affect the ability of females to show male-like sexual activity in response to exogenous androgenic stimulation.     

Effects of ventromedial and lateral hypothalamic stimulation on chemically-induced liver injury in rats

The effects of hypothalamic stimulation on experimental liver injury induced by carbon tetrachloride (CCl4) or dimethylnitrosamine (DMN) were studied in rats, by measuring plasma alanine aminotransferase (ALT) activity as an index of acute liver injury. Electrical stimulation of the ventromedial hypothalamus (VMH) in CCl4-treated rats caused a marked increase in plasma ALT activity, accompanied by a significant decrease in ALT activity in the liver, although CCl4 treatment alone had no significant effect on plasma ALT activity. A similar effect of VMH stimulation on plasma ALT activity was observed in rats treated with DMN, another hepatotoxic chemical. No such exaggerated effect of VMH stimulation on plasma ALT activity was observed after stimulation of the lateral hypothalamic area (LH). Surgical sympathetic denervation of the liver greatly suppressed the increase in plasma ALT activity after CCl4 injection and VMH stimulation. Measurement of regional blood flow indicated that VMH stimulation did not produce a significant change in blood flow to the liver. These results suggest that the VMH is involved in the progress of chemically-induced liver injury through activation of the sympathetic nerve (hepatic nerves), possibly by affecting liver metabolism more than the blood flow change to the liver.     

神经降压素对刺激下丘脑减压区所致减压反应的影响

大鼠下丘脑前部一侧减压区,采用直流方波或化学刺激、注射微量神经降压素及其抗血清和放射免疫分析等方法,探讨了神经降压素对刺激该减压区所致减压反应的影响。结果表明：（１）电或化学刺激该减压区,可出现同其它哺乳动物相似的减压反应;（２）该减压区注射微量神经降压素,可使电刺激该减压区所致的减压反应明显增强;反之,注射抗神经降压素血清,该减压反应明显抑制;（３）电刺激该减压区,可使下丘脑和血浆中的神经降压素免疫活性物含量明显增高。结果提示,神经降压素可能参与电刺激该减压区所致的减压反应过程。     

Gastrin in the mechanisms of genetic determination of feeding behavior in rabbits

Spreading of a dominant motivation to the molecular intracellular mechanisms of genetic memory was studied. Blockage of protein synthesis in the nervous system selectively abolishes food motivation in rabbits during stimulation of the lateral hypothalamus but exerts no noticeable effect on avoidance responses during stimulation of the ventromedial hypothalamus. During protein synthesis blockage, food motivation returns to normal upon pentagastrin intracerebroventricular (i.c.v.) injection. Intracerebroventricular administration of antigastrin immunoglobulin inhibits feeding reaction to lateral hypothalamic stimulation but not avoidance response to ventromedial hypothalamic stimulation. It was concluded that feeding motivation translates into feeding behavior in the following stages: motivational excitation, gene activation, mRNA synthesis, formation of a gastrin-like peptide, and expression of feeding behavior.     

Spread of excitation from the ventromedial hypothalamus to the limbic-reticular structure of the brain

The sequence of origination of the evoked potentials in different regions of the septum amygdale and the reticular formation in response to the gradually increasing stimulation of the hypothalamic ventromedial nucleus was studied. As demonstrated, excitation that initially occurs in the hypothalamic ventromedial nuclei embraced first the structures of the septum and rostral reticular formation and then more caudal region of the reticular formation and amygdala.     

Glucagon-related peptides in the rat hypothalamus

Summary Immunohistochemically, nerve fibers and terminals reacting with anti-N-terminal-specific but not with anti-C-terminal-specific glucagon antiserum were observed in the following rat hypothalamic regions: paraventricular nucleus, supraoptic nucleus, anterior hypothalamus, arcuate nucleus, ventromedial hypothalamic nucleus and median eminence. Few fibers and terminals were demonstrated in the lateral hypothalamic area and dorsomedial hypothalamic nucleus. Radioimmunoassay data indicated that the concentration of gut glucagon-like immunoreactivity was higher in the ventromedial nucleus than in the lateral hypothalamic area. In food-deprived conditions, this concentration increased in both these parts. This was also verified in immunostained preparations in which a marked enhancement of gut glucagon-like immunoreactivity-containing fibers and terminals was observed in many hypothalamic regions. Several immunoreactive cell bodies were found in the ventromedial and arcuate nuclei of starved rats. Both biochemical and morphological data suggest that glucagon-related peptides may act as neurotransmitters or neuromodulators in the hypothalamus and may be involved in the central regulatory mechanism related to feeding behavior and energy metabolism.     

The significance of hyperphagia and diet composition on the metabolism in ventromedial hypothalamic lesioned male rats

The metabolic consequences of ventromedial hypothalamic lesion were studied in a group of aged male rats which were obese and had decreased response to insulin. The effects of hyperphagia and ventromedial hypothalamic lesion per se were separated by comparing experimental animals fed isocalorically with controls and animals fed ad libitum. Ventromedial hypothalamic lesion as such led to increases in the glucose conversion to fatty acid and in lipoprotein lipase activity in adipose tissue. Protein catabolism as reflected by plasma urea levels, was enhanced. The lipoprotein lipase activity in heart tended to be lower after VMH lesion. These metabolic changes were amplified in the VMH lesioned rats fed ad libitum. The liver glycogen content was lowered by VMH lesion, but this effect was abolished by hyperphagia. In parallel experiments the influence of diet composition was studied by feeding similar groups with diet of high fat content. The glucose incorporation in fatty acids was in all groups markedly and similarly inhibited by the high fat diet. The increase in lipoprotein lipase activity in heart and adipose tissue of control rats with high fat intake could not be demonstrated in any of the groups with ventromedial hypothalamic lesion. The plasma urea level in the control group was not affected by the diet, but tended to increase in the ventromedial hypothalamic lesioned groups on high fat intake. These findings demonstrate that the well known metabolic effects of ventromedial hypothalamic lesions are also manifest in obese insulin resistant male rats. Furthermore, the responses to changes in diet composition are different from those of the control rats.     

Participation of adrenal hormones in the genesis of arterial hypertension of hypothalamic origin]

Continuous many-hour stimulation of the hypothalamic negative emotiogenic centres (ventromedial nuclei) evoked a stable arterial hypertension with a peculiar phasic dynamics of the adrenal secretory activity in waking immobilized rabbits. Bilateral extirpation of the adrenal glands decreased the initial level of the average arterial pressure, inhibiting development of stable arterial hypertension. Many-hour stimulation of the mentioned structures also produced stable arterial hypertension in adrenalectomized rabbits if preceded by the administration of hydrocortisone together with adrenaline. Against the background of separate administration of hydrocortisone and adrenaline to adrenalectomized rabbits, many-hour stimulation of the ventromedial hypothalamus evoked a short-term rise in the arterial pressure. A conclusion was drawn that activation of hormones of the adrenal cortical and medullary layers played an important part in the formation of stable arterial hypertension in rabbits under continuous many-hour stimulation of the hypothalamic negative emotiogenic centres.     

Expression of c-Fos gene in the rat hypothalamus upon electric painful stimulation and EHF irradiation of the skin

Studies of the activation pattern of hypothalamic cells upon electric painful stimulation have revealed an increase in the counts of c-Fos-positive cells (72.02-98.95%) predominantly of a size ranging from 10 to 50 microm2. EHF irradiation of the skin activates hypothalamic cells of the size ranging from 10 to 70 microm2 in the paraventricular, dorsomedial nuclei, and in perifonical zone of the lateral hypothalamic area. The combined action of EHF skin irradiation and electric painful stimulation leads to a decrease in the counts of cells activated in result of the painful stimulation in the anterior hypothalamic area, ventromedial nucleus, and the basal part of the lateral area. Changes in size distributions of activated cells are found in the ventromedial nucleus and the basal part of the lateral area, occur mainly through decreased counts of smaller cells (10-30 microm2) and increased counts of lager cells. The modulatory effect of EHF irradiation of the skin was found to be expressed as a reduction in hypothalamic cell activation caused by electric painful stimulation.     

Ultrastructural localization of the receptor for leptin in the rat hypothalamus

Ultrastructural localization of the leptin receptor in the rat hypothalamus was studied by immunocytochemistry. The antiserum against the leptin receptor which was used specifically recognized the carboxy terminal of the cytoplasmic domain. Intense leptin receptor immunoreactivity was detected in the arcuate, paraventricular, and ventromedial nuclei of the hypothalamus and in the lateral hypothalamic area. At the ultrastructural level, leptin receptor-like immunoreactivity appeared to be concentrated predominantly in perikarya and dendrites of these areas and strong immunolabeling for the leptin receptor was detected in the plasma membrane, rough endoplasmic reticulum, Golgi apparatus, and cytoplasmic matrix. This study provides the first detailed fine structure of leptin receptor-immunoreactive neurons in the rat hypothalamus. It may help to provide better understanding of the functions of leptin in the rat hypothalamus.     

Fos Expression in the Rat Brain After Intraperitoneal Injection of Staphylococcus Enterotoxin B and the Effect of Vagotomy

The current study was designed to locate the neuronal activation in rat brain following intraperitoneal injection of Staphylococcus enterotoxin B (SEB) and observe the consequence of preliminary subdiaphragmatic vagotomy on SEB-induced brain Fos expression to clarify the role of the vagus nerve in sensation and transmission of abdominal SEB stimulation. The results showed that intraperitoneal SEB (1 mg/kg) induced a robust Fos expression in widespread brain areas. A significant increase of Fos immunoreactive cells were observed in the solitary tract nucleus, locus ceruleus, lateral parabrachial nucleus, ventrolateral part of central gray, medial amygdaloid nucleus, central amygdaloid nucleus, ventromedial part of thalamus, dorsomedial part of thalamus, hypothalamic paraventricular nucleus, lateral habenula, and lateral septum nucleus following SEB challenge. In hypothalamic paraventricular nucleus, in addition to the dense Fos expression in the parvocellular portion, some Fos-positive cells were also observed in the anterior magnocellular nucleus of the complex. Double immunofluorescence studies showed that these Fos-immunoreactive cells were mostly oxytocinergic. The results also showed that subdiaphragmatic vagotomy largely attenuated, but not totally abrogated, the brain Fos expression induced by abdominal administration of SEB. Our data suggest that peripheral SEB stimulation can induce activation of neurons in widespread brain areas and that the vagus plays a crucial role in transmitting the signal of abdominal immune stimulation to the brain.     

刺激下丘脑腹内侧核引起的心脏收缩性变化

本文在麻醉猫上,采用LVSP、dp/dt_(max)、V_(max)及心力环等指标,研究了刺激下丘脑腹内侧核(VMH)及其与第三脑室之间的VMH内侧邻近区(L_(0.5)引起的心脏收缩性改变。刺激VMH引起心力增强,刺激VMH内侧邻近区(L_(0.5)使心力减弱。切断两侧迷走神经后,不影响上述反应。实验结果表明:调节心脏变力性与变时性的机能结构于下丘脑某些区域中是分别存在的。     

Effects of hypothalamic and amygdaloid stimulation on reaching behaviour in the rat

Thirty adult rats were trained in a reaching behaviour schedule, after which bipolar steel electrodes were bilaterally implanted into the ventromedial hypothalamus (VMH), lateral hypothalamic area (LHA) or basolateral amygdala (BLA). On subsequent training sessions, these structures were electrically stimulated employing a movement-synchronized stimulation design. The results show that VMH stimulation produces aversive effects: the animals go away from the feeder after the first stimulus. Reaching impairment resulting from LHA or BLA stimulation mainly affected the grasping phase; additionally, repetition of movement sequence was observed. The results are discussed in the framework of Kornhuber's concept of preprogrammed ballistic movements.     

Involvement of peptide histidine isoleucine (PHI) in prolactin secretion induced by serotonin in rats

The possible role of hypothalamic peptide histidine isoleucine (PHI) in prolactin (PRL) secretion induced by serotoninergic mechanisms was investigated in male rats using a passive immunization technique. Intracerebroventricular injection of serotonin (5HT, 10 micrograms/rat) raised plasma PRL levels both in urethane-anesthetized rats and in conscious rats pretreated with normal rabbit serum (0.5 ml/rat, iv, 30 min before). Plasma PRL responses to 5HT were blunted in these animals when they were pretreated with rabbit antiserum specific for PHI (0.5 ml/rat, iv, 30 min before) (mean +/- SE peak plasma PRL: anesthetized rats 271.3 +/- 38.3 ng/ml vs 150.0 +/- 12.6 ng/ml, p less than 0.01, conscious rats 54.3 +/- 6.8 ng/ml vs 30.7 +/- 4.1 ng/ml, p less than 0.025). These results suggest that hypothalamic PHI is involved, at least in part, in PRL secretion induced by central serotoninergic stimulation in the rat.     

Site of action for β-endorphin-induced changes in plasma luteinizing hormone and prolactin in the ovariectomized rat

A number of sites have been hypothesized as loci at which opioid substances act to alter the secretion of luteinizing hormone (LH) and prolactin (PRL) (1–8). The aim of the present study was to determine the site(s) at which the opioid peptide β-endorphin (β-END) acts to influence plasma LH and PRL levels in the ovariectomized (OVX) rat. β-END, administered into the third ventricle of conscious OVX rats fitted with jugular catheters, significantly decreased plasma LH in doses ? 50 ng and increased PRL levels at all doses administered (10, 50, 100 and 250 ng) in a dose dependent fashion. To identify possible central nervous system sites of action, 250 ng β-END was unilaterally infused into various brain sites. Plasma LH was significantly decreased and plasma PRL significantly increased by infusions into the ventromedial hypothalamic area, the anterior hypothalamic area, and the preoptic-septal area. There was no significant effect of β-END infusions into the lateral hypothalamic area, amygdala, midbrain central gray, or caudate nucleus. When hemipituitaries of OVX rats were incubated $\text{in}$$\text{vitro}$ with β-END (10^?7M to 10^?5M), there was no suppression of basal or LHRH-induced LH release, nor was there any alteration of basal PRL release. It is concluded that β-END acts at a medial hypothalamic and/or preoptic-septal site and not the pituitary, to alter secretion of LH and PRL.     

Study of electrical activity in the area of the hypothalamic ventromedial nucleus and the lateral hypothalamus of rats fed on a high protein and high fat diet.

The authors studied bioelectric potentials in the area of the hypothalamic ventromedial nucleus and the lateral hypothalamus of rats fed on a standard, a high protein and a high fat diet. On the first 3--6 days after changing from the standard to the high fat and high protein diets, a decrease in the amplitude of electrical activity was recorded in both the areas in question. It was also found that the frequency of electrical activity in the hypothalamic ventromedial nucleus or the lateral hypothalamus rose, after 3 days administration of the high fat or the high protein diet, in correlation to the type of diet, and that, in the frequency spectrum, a change occurred in the proportion of basic frequency in relation to superimposed frequencies distorting it. It was further found that there was a permanent difference between the amplitude of electrical activity in the lateral hypothalamus and the hypothalamic ventromedial nucleus.     

The hypothalamo-pancreatic axis: evidence for a neurohormonal pathway in the control of the release of insulin and glucagon.

Segments of freshly dissected rat hypothalamic tissue corresponding to the ventrolateral (VLH) and ventromedial (VMH) regions were incubated in Gey and Gey medium at 37 C under 95% O2 and 5% CO2 for 30 minutes. Groups of male rats which had been fasted for 6 hours received injections (i.v.) of either VMH medium or VLH medium while a third group received control medium only. Blood samples were taken from the aorta 3 minutes post-injection and circulating levels of insulin and glucagon were determined by RIA. The medium from the incubation of the VMH tissue significantly elevated glucagon levels and significantly lowered plasma concentrations of insulin compared to the levels in animals receiving injections of control medium. The hormone levels in animals receiving an injection of medium in which VLH tissue had been incubated did not differ significantly from the controls. In another type of experiment VMH medium, but not VLH medium, was able to overcome the somatostatin-induced inhibition of glucagon release. These observations suggest that hypothalamic factors may be involved in the regulation of the endocrine pancreas.     

电刺激兔下丘脑不同部位诱发的房性心律失常

在57只麻醉家兔,用同心圆双极电极刺激右侧下丘脑外侧区、前区、后区、背内侧核、腹内侧核五个不同部位,观察到均能诱发房性早搏等房性心律失常,且存在相对特异性。在用1mA 强度电刺激时,以前三个部位的诱发率较高。如预先轻度灼伤右心房后再刺激下丘脑外侧区或前区,可显著提高房性心律失常的发生率,并使诱发房颤等严重房性心律失常的机会有所增加。在同时描记股动脉血压的家兔中,观察到房性心律失常均在血压增高时出现,并以下丘脑后区、前区、外侧区的增压反应较为显著。在下丘脑外侧区增加刺激强度时,房性心律失常的发生率不随增压平均值的增加而递增,与室性心律失常不同。切断双侧颈迷走神经干后再刺激下丘脑同一部位时,原能诱发房性早搏的家兔全部不再诱发,而原能诱发以室性早搏为主的室性心律失常的部分兔仍能发生。这些结果提示,电刺激下丘脑诱发房性心律失常的机制与室性心律失常有所不同。     

Hypothalamic influences on unit activity in the cat superior colliculus

Experiments on immobilized unanesthetized cats showed that hypothalamic stimulation effectively modified spontaneous unit activity and activity evoked by photic stimulation in the superior colliculus. Long-latency responses, often with a tonic type of formation, were predominant. Meanwhile, definite differences were found in the character of influences from different regions of the hypothalamus. Stimulation of the anterior hypothalamic region and lateral hypothalamus led more frequently to inhibition of spontaneous activity, often expressed as the development of initial inhibition, especially during stimulation of the lateral hypothalamus. Definite modulation of spontaneous activity of cyclic type also developed. Influences from these structures on activity evoked by photic stimulation were chiefly facilitatory and modulating in character. Stimulation of the ventromedial nucleus could produce inhibitory and facilitatory effects equally on activity of tectal neurons, with a tendency for the frequency of manifestation of facilitation to increase when a series of stimuli was used. The mechanisms of triggering and realization of hypothalamic influences on activity in the superior colliculus are discussed.Ivano-Frankovsk State Medical Institute, Ministry of Health of the Ukrainian SSR. Translated from Neirofiziologiya, Vol. 11, No. 6, pp. 560–568, November–December, 1979.