Enhancement and suppression of self-stimulation after ventromedial hypothalamic lesions.

Investigated the effects of lesions in the ventromedial hypothalamus (VMH) upon self-stimulation in 25 male hooded Long-Evans rats. Ss trained to press a bar for lateral hypothalamic (LH) stimulation showed an enhancement of responding during the 1st 24 hrs after VMH lesioning, followed by a suppression of responding for several days. The degree of response suppression, but not enhancement, was correlated with an increase in food intake. In Ss trained to shuttle for LH stimulation, only the suppression effect was observed after VMH lesions. Barpressing for dorsal tegmental stimulation was not affected by the lesions. Results suggest that LH stimulation activates at least 2 groups of neurons: one group is specifically involved in barpressing and the other is involved equally in barpressing and shuttling. (French summary) (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Proximal occlusion of the dominant anterior cerebral artery for anterior communicating aneurysm

A series of six experiments examined the neural loci responsible for caerulein's suppression of eating. Caerulein is a decapeptide chemically and physiologically similar to cholecystokinin, a naturally occurring gut hormone in rats. Rats with lesions in the ventromedial hypothalamus (VMH) showed reduced sensitivity to caerulein (1 mug/kg); rats with lateral hypothalamic (LH) destruction showed heightened sensitivity. Microinjections of caerulein into the VMH, but not into the LH, limited feeding. Finally, tritiated caerulein was selectively bound to tissue in the VMH. The results are discussed in terms of the hypothesis that the VMH manages postprandial inhibition in the rat.     

Ventromedial hypothalamus and short-term feeding suppression by caerulein in male rats.

A series of 6 experiments with 88 male Sprague-Dawley rats examined the neural loci responsible for caerulein's suppression of eating. Caerulein is a decapeptide chemically and physiologically similar to cholecystokinin, a naturally occurring gut hormone in rats. Ss with lesions in the ventromedial hypothalamus (VMH) showed reduced sensitivity to caerulein (1 mug/kg); Ss with lateral hypothalamic (LH) destruction showed heightened sensitivity. Microinjections of caerulein into the VMH, but not into the LH, limited feeding. Finally, tritiated carulein was selectively bound to tissue in the VMH. Results are discussed in terms of the hypothesis that the VMH manages postprandial inhibition in the rat. (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Glucose-induced intracellular ion changes in sugar-sensitive hypothalamic neurons

In the lateral hypothalamic area (LHA) of rat brain, approximately 30% of cells showed sensitivity to small changes in local concentrations of glucose. These "glucose-sensitive" neurons demonstrated four types of behavior, three of which probably represent segments of a continuous spectrum of recruitment in response to ever more severe changes in blood sugar. Type I cells showed maximum activity 相似文献   

Multiple knife cuts between the medial and lateral hypothalamus in the rat: A reevaluation of hypothalamic feeding circuitry.

In 2 experiments single or multiple sets of bilateral knife cuts were made in a total of 73 female CFE rats just lateral to the ventromedial hypothalamus (VMH) and/or just medial to the lateral hypothalmus (LH). The lateral VMH knife cuts by themselves produced greater hyperphagia and obesity than did the medial LH cuts. The lateral VMH knife cuts also significantly increased food intake and body weight in Ss previously given bilateral cuts along the medial LH border. Findings indicate that the feeding inhibitory fibers responsible for the hyperphagia syndrome do not project from the VMH to the LH, and this calls for a reevaluation of hypothalamic circuitry. It was also discovered that sham surgery in 7 Ss had a significant suppressive effect on the hyperphagia syndrome produced by hypothalamic knife cuts. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Food intake and lateral hypothalamic self-stimulation covary after medial hypothalamic lesions or ventral midbrain 6-hydroxydopamine injections that cause obesity.

In rats with perifornical lateral hypothalamic (LH) electrodes that induced feeding, self-stimulation through the same electrodes increased immediately after ventromedial hypothalamic (VMH) lesions and did not return to normal until food intake normalized and the rats had become obese. A unilateral far-LH lesion decreased feeding and contralateral perifornical LH self-stimulation. 6-hydroxydopamine (6-OHDA) injected into the midbrain to destroy the ventral noradrenergic bundle (VNAB) caused hyperphagia and increased LH self-stimulation. In summary, VMH or VNAB damage increased feeding and self-stimulation; contralateral far-LH damage decreased both. Results confirm the earlier suggestion that the VMH region is necessary for normal inhibition of feeding and feeding reward as reflected in self-stimulation rate. Although massive 6-OHDA-induced depletion of the dopamine system that passes through the LH can cause starvation and impair self-stimulation, results suggest that selective catecholamine depletion of ventral midbrain neurons with sparing of the A9 and A10 dopaminergic cells can disinhibit feeding and self-stimulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Thiamin deprivation in ventromedial hypothalamic hyperphagic rats: Anorexia, specificity of food aversion, and a dietary consideration.

In 3 studies, the anorexic consequence of thiamine deprivation was investigated in ventromedial hypothalamic (VMH) hyperphagic CD male rats under either high-fat or low-fat (HF and LF, respectively) thiamine-free diet conditions. The LF diet maintained feeding significantly longer in thiamine-deprived VMH Ss than in intact Ss, whereas the HF diet sustained feeding in thiamine-deficient intact Ss and accelerated anorexia onset in vitamin-B1-deprived VMH Ss. This effect was noted under both ad lib and pair-feeding conditions. Thiamine-deprived VMH Ss subjected to weight control developed anorexia sooner than intact Ss regardless of the diet employed. The VMH Ss fed an HF diet failed to resume feeding after thiamine readministration, which is interpreted as a permanent aversion to this diet. The relation between dietary intake and conditioned taste aversion is discussed with reference to the VMH and intact rats. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hyperinsulinemia in rats with ventromedial hypothalamic lesions: Role of hyperphagia.

Examined the relation of hyperinsulinemia to hyperphagia in 18 female hooded Long-Evans rats with lesions of the ventromedial hypothalamus (VMH). Plasma insulin and glucose levels were assayed after a 4-hr fast and 17 min after the initiation of a meal (6 ml of sweetened milk in 7 min) in 8 other Ss with sham lesions, VMH Ss maintained at preoperative body weight by food restriction, and VMH Ss fed ad lib. Both VMH groups displayed basal and postabsorptive hyperinsulinemia compared with the sham-operated group, but insulin levels were greatest under the ad lib feeding condition. It is suggested that VMH hyperinsulinemia is due both to a primary effect of the lesion and to hyperphagia and that marked obesity can result in the absence of basal hyperinsulinemia as a result of hyperphagia with consequent postabsorptive hyperinsulinemia. (14 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Functional perineal colostomy with pudendal nerve anastomosis following anorectal resection: a cadaver operation study on a new procedure

Intranulear microinjection and electrical stimulation technique were employed to evaluate the effect of ventromedial hypothalamus (VMH) on the gastric inhibition elicited by basomedial amygdala nucleus (BMA) excitation. The results were as follows: (1) Microinjections of CCk-8 (50 ng/microliter) into bilateral BAM resulted in significant decrease in intragastric pressure (IGP) and gastric motility frequency (GMF) (P < 0.01). (2) Neither CCK-A receptor antagonist [L364, 718] nor CCK-8 receptor antagonist [L365, 260] induced effects on IGP or GMF when given alone. (3) If bilateral BMA were pretreated with [L364, 718], CCK-8 could no longer induce any inhibitory effects, whlie [L365, 260] had no similar suppressive effect. (4) The inhibitory effects were not found in other nuclei in the amygdaloid body, such as bed nucleus of the stria terminalis intramygdaloid (BSTIA) and amygdaloid nucleus medial (Me). (5) Electrical stimulation of unilateral VMH or BMA would result in the inhibition of IGP and GMF. (6) After electric coagulation of VMH unilateraly injection of CCK-8 to or stimulation of homolateral VMH could no longer inhibite IGP or GMF. The above results suggest that in BMA CCK-8 exerts inhibitory effect on both motility and intragastric pressure through CCK-A receptors.     

Particulate air pollution and daily mortality: can results be generalized to Latin American countries?

In a series of studies on histaminergic functions in the hypothalamus, probes to manipulate activities of histaminergic neuron systems were applied to assess its physiologic and pathophysiologic implications using non-obese normal and Zucker obese rats, an animal model of genetic obesity. Food intake is suppressed by either activation of H1-receptor or inhibition of the H3-receptor in the ventromedial hypothalamus (VMH) or the paraventricular nucleus, each of which is involved in satiety regulation. Histamine neurons in the mesencephalic trigeminal sensory nucleus modulate masticatory functions, particularly eating speed through the mesencephalic trigeminal motor nucleus, and activation of the histamine neurons in the VMH suppress intake volume of feeding at meals. Energy deficiency in the brain, i.e., intraneuronal glucoprivation, activates neuronal histamine in the hypothalamus. Such low energy intake in turn accelerates glycogenolysis in the astrocytes to prevent the brain from energy deficit. Thus, both mastication and low energy intake act as afferent signals for activation of histaminergic nerve systems in the hypothalamus and result in enhancement of satiation. There is a rationale for efficacy of a very-low-calorie conventional Japanese diet as a therapeutic tool for weight reduction. Feeding circadian rhythm is modulated by manipulation of hypothalamic histamine neurons. Hypothalamic histamine neurons are activated by an increase in ambient temperature. Hypothalamic neuronal histamine controls adaptive behavior including a decrease in food intake and ambulation, and an increase in water intake to maintain body temperature to be normally constant. In addition, interleukin-1 beta, an endogenous pyrogen, enhanced turnover of neuronal histamine through prostaglandin E2 in the brain. Taken together, the histamine neuron system in the hypothalamus is essential for maintenance of thermoregulation through the direct and indirect control of adaptive behavior. Behavioral and metabolic abnormalities of obese Zucker rats including hyperphagia, disruption of feeding circadian rhythm, hyperlipidemia, hyperinsulinemia, and disturbance of thermoregulation are essentially derived from a defect in hypothalamic neuronal histamine. Abnormalities produced by depletion of neuronal histamine from the hypothalamus in normal rats mimic those of obese Zuckers. Grafting the lean Zucker fetal hypothalamus into the obese Zucker pups attenuates those abnormalities. These findings indicate that histamine nerve systems in the brain play a crucial role in maintaining homeostatic energy balance.     

Effects of chronic intrahypothalamic infusion of insulin on food intake and diurnal meal patterning in the rat.

In Experiment 1, rats were chronically infused with insulin (2.7, 27, or 270 ng/hr) or 0.9% saline into the ventromedial (VMH), medial perifornical (PF), or lateral (LH) hypothalamus. VMH infusions of insulin caused a significant, dose-dependent decrease in food intake and body weight; PF infusion of insulin was less effective, but significant; whereas LH infusions of insulin were ineffective. In Experiment 2, rats were chronically infused with insulin (0.54 ng/hr) or 0.9% saline into the VMH, paraventricular (PVN), or posterior (PN) hypothalamic nucleus. Subjects that received VMH or PN infusions of insulin failed to regain weight lost as a result of surgery even 2 weeks after infusion; subjects that received PVN infusions of insulin regained their preoperative weights faster than did controls. All of the groups that received insulin significantly increased their daytime food intake during the infusion period and decreased their night food intake slightly; 24-hr food intake remained unchanged. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Feeding and drinking pathways between medial and lateral hypothalamus in the rat.

Carried out 3 experiments, using 101 female rats of the CFE strain. Bilateral parasagittal transections were made at different lateral and dorsal-ventral positions in and between the ventromedial hypothalamus (VMH) and lateral hypothalamus (LH). Cuts through or just lateral to the VMH produced hyperphagia and obesity, while cuts through or medial to the LH produced, depending upon their exact position and the diet, either temporary aphagia-hypophagia, mild hyperphagia, or no effect. The cuts medial to the LH, but not the others, abolished insulin-induced eating. All cuts produced deficits in drinking regulation that varied according to their exact position. These deficits included hypodipsia, mild hyperdipsia, and reduced water/food ratios, as well as reduced drinking responses to food deprivation, water deprivation, hypertonic sodium chloride injections, and polyethylene glycol injections. The knife cuts also produced changes in gustatory reactivity. The hypothalamic pathways responsible for these effects are discussed. (54 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neural levels of cholecystokinin peptide and mRNA during dietary stimulation of growth and LH secretion in growth-retarded lambs

Chronic feed restriction of prepubertal male lambs adversely affects reproductive development by inhibiting the pulsatile release of luteinizing hormone (LH). Because this effect can be reversed by ad libitum feeding, the associations between diet-induced increases in LH release and concurrent changes in body weight gain, serum glucose. CCK peptide, and CCK mRNA were examined. Neonatally castrated male lambs received a restricted ration to maintain their respective weaning weights beginning at 8 wk of age. At 23 wk of age, lambs were assigned randomly to receive additional feed equivalent to 0%, 50%, or 100% of their previous daily intake. Serum profiles of LH and glucose were determined 2 and 4 wk after onset of the increased intakes. At 27 wk of age, lambs were euthanized and both hypothalamic and cerebral cortical tissues were collected for analysis of CCK peptide and CCK mRNA. With additional intakes, body weight gain increased (P < 0.001) proportional to the graded increases in feed intake. Mean serum LH concentrations, LH peak frequencies, and serum glucose concentrations also increased (P < 0.05) progressively among the 0%, 50%, and 100% dietary intake groups. Neither CCK peptide nor CCK mRNA differed (P > 0.05) among dietary groups suggesting that endogenous CCK in the whole hypothalamus did not change with the feeding-induced increase in LH release. Concentrations of CCK peptide in cerebral cortex were greater (P < 0.05) than hypothalamic concentrations, but there were no differences between hypothalamus and cerebral cortex in the relative abundance of CCK mRNA. In summary, dietary stimulation of growth-retarded male lambs resulted in progressive increases in body weight gain, mean serum LH, serum glucose, and LH peak frequencies. Because hypothalamic levels of CCK peptide and CCK mRNA did not change during feeding-induced secretion of LH, endogenous CCK in the hypothalamus seems unlikely as a chronic mediator of nutrition-sensitive LH release.     

Interpretation of the oblique Abrikosov flux lattice in YBa2Cu3O7

We investigated to find which types of neuronal disturbance in the hypothalamus are responsible for ventromedial hypothalamic nucleus (VMH) lesion-induced development of obesity. We found that in VMH-lesioned obese rats, the contents of norepinephrine (NE) and dopamine in the hypothalamus were selectively decreased, but that the serotonin and acetylcholine levels were unchanged from those in sham controls. Also, the content of NE in the lateral portion of the hypothalamus was decreased. Our results show that disturbance of the hypothalamic noradrenergic and dopaminergic neurons, but not of the serotonergic or cholinergic neurons, contributes to the development of VMH lesion-induced obesity.     

Involvement of brain CCK in the adaptation of gut motility to digestive status and stress: a review

Cholecystokinin is involved at both central and peripheral level in the control of gut motility. At CNS level, CCK8 appears to play a major role in the adaptation of duodeno-jejunal motility to the postprandial state, ie the disruption of the migrating motor complex. CCK8 microinjected into the ventro-medial nucleus of the hypothalamus (VLH) induces a fed-like pattern not reproduced by similar administration into the hypothalamus. Furthermore, CCKA antagonists such as devazepide injected into the VMH just prior to the meal shortens the duration of the postprandial pattern of activity, an effect not reproduced by similar injection into the LH. Similarly the colonic motor activation observed after feeding is suppressed by devazepide injected into the VMH in rats. In addition, icv administration of CCKA but not CCKB receptor antagonist prevents meal- and CCK8-induced colonic hyperkinesia in dogs. In rats, emotional stress is associated with an increase in colonic motility related to the central release of CRF. We have shown that CCK8 injected centrally, at a lower dose than that producing an increase in colonic motility, is able to prevent stress-induced colonic motor alteration.     

Conditioned taste aversion in lean and obese rats with ventromedial hypothalamic knife cuts.

Assessed the development of a conditioned taste aversion (CTA) in 60 female Sprague-Dawley rats made hyperphagic with parasagittal knife cuts in the ventromedial hypothalamus (VMH). Ss were water deprived and presented with a .1% saccharin solution paired with injections of either LiCl or NaCl. In Exp I, VMH Ss tested at a nonobese weight level did not differ from sham-operated controls in acquisition and extinction of the CTA. In Exp II, moderately obese VMH Ss displayed a stronger CTA than did sham-operated controls as evidenced by slower extinction. A 2nd group of obese VMH Ss given an amount of LiCl equivalent to that given to the controls also displayed retarded extinction of the CTA. Results reflect an obesity-induced suppression in appetitive motivation. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Active regulation to be lean by rats with ventromedial hypothalamic lesions.

52 adult female Long-Evans rats with electrolytic or radio-frequency thermocoagulatory lesions of the ventromedial hypothalamus (VMH) lived on pellet fragments or powdered chow containing as much as 1.2% quinine sulfate or lived in Skinner boxes with 45-mg pellets delivered contingent on FRs of leverpressing up to FR 128. Body weights maintained by VMH Ss were determined by the percentage of quinine in or the contingency of reinforcement of the food on which they lived. Even when Ss lived on highly adulterated or response-contingent food and were lean, they ate more of that food when the ambient temperature was reduced and less of that food during several weeks of forced feeding of eggnog. Weight maintenance in the cold and caloric compensation during forced feeding were as precise for VMH Ss eating highly adulterated chow or Noyes pellets contingent on high FRs as for VMH Ss eating laboratory chow ad lib, even though the former Ss at the time maintained weights no greater than intact Ss and the latter Ss were grossly obese. Regulation in the cold or during forced feeding was only a little less precise for Ss with lesions than for intact Ss. It may be as characteristic of VMH Ss that they eat to become lean and remain lean as that they eat to be obese. (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The anti-gonadotropic effects of cytokines: the role of neuropeptides

The inhibitory effect of inflammation and endotoxins on the secretion of reproductive hormones from the hypothalamo-pituitary axis is well documented. A comparison of the luteinizing hormone (LH) suppressing effects of several pro-inflammatory cytokines revealed that centrally administered IL-1 beta was the most potent inhibitor of pituitary LH secretion; interleukin (IL)-1 alpha and tumor necrosis factor (TNF) alpha were relatively less effective, whereas IL-6 was ineffective. This order of potency suggested that the anti-gonadotropic effects of an immune challenge are most likely attributable to the action of centrally released IL-1 beta, and this was supported by the demonstration that IL-1 beta suppressed hypothalamic luteinizing hormone releasing hormone (LHRH) release. We used a multifaceted approach to identify the afferent signals in the brain that convey immune messages to hypothalamic LHRH neurons. Pharmacological studies with specific antagonists of opioid receptor subtypes demonstrated that activation of the mu 1 receptor subtype was required to transmit the cytokine signal. Furthermore, icv IL-1 beta upregulated hypothalamic POMC mRNA and increased the concentration and release of beta-endorphin, the primary ligand of mu 1 receptors. We have obtained evidence that IL-1 beta also enhanced the gene expression and concentration of tachykinins, a family of nociceptive neuropeptides in the hypothalamus. Blockade of tachykinergic NK2 receptors attenuated IL-1 beta induced inhibition of LH secretion. Collectively, these results demonstrate that IL-1 beta, generated centrally in response to inflammation, upregulates the opioid and tachykinin peptides in the hypothalamus. These two groups of neuropeptides are critically involved in relaying the cytokine signal to neuroendocrine neurons and causing the suppression of hypothalamic LHRH and pituitary LH release.     

The second messenger cAMP elicits eating by an anatomically specific action in the perifornical hypothalamus

We have previously shown that a membrane-permeant analog of cAMP, 8-bromo-cAMP (8-br-cAMP), elicits a vigorous eating response when microinjected into the perifornical hypothalamus (PFH) or lateral hypothalamus (LH) of satiated rats, suggesting that increases in cAMP in these areas may be important in the neural control of eating. To determine the locus of this effect, we compared the ability of 8-br-cAMP (1-100 nmol/0.3 microl) to elicit eating after microinjection into the PFH, LH, or the following bracketing areas: the anterior and posterior LH, paraventricular nucleus of the hypothalamus, thalamus, and amygdala. 8-br-cAMP at 50 nmol elicited eating (>/=3.4 gm in 2 hr) exclusively in the PFH and LH. At 100 nmol, 8-br-cAMP elicited a larger response in these areas and elicited a smaller, more variable response in the thalamus. We similarly mapped the feeding-stimulatory effects of compounds that increase endogenous cellular cAMP in naive rats. Combined microinjection of matched doses (300 nmol) of 3-isobutyl-1-methylxanthine and 7-deacetyl-7-O-(N-methylpiperazino)-gamma-butyryl-forskolin was effective exclusively in the PFH, eliciting an average 2 hr food intake of 8.4 +/- 2.0 gm. Collectively, these results suggest that increases in cellular cAMP within a specific brain site, the PFH, may play a role in the neural stimulation of eating.     

The effect of stimulation of the lateral hypothalamus on the spike trains of the rabbit neocortical neurons

Cross- and autocorrelation histograms of the impulse activity of the visual and sensorimotor cortical neurons were plotted before and after stimulation of the right (RH) and left lateral hypothalamus (LH) which provoked food motivation reactions. Reorganization in correlated activity of neocortical neurons was more expressed after the LH than the RH stimulation. Only after the LH stimulation the number of neuronal pairs with co-related activity in the left hemisphere increased by 41% and some order of priority appeared in the neuronal discharges. The visual neurons discharged after the sensorimotor ones with delays up to 120 ms. The conclusion was drawn that cortical interhemispheric asymmetry of electrical activity during hunger was associated with unequal operation of the right and left lateral hypothalamus.