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)     

Hypothalamic and midbrain neural pathways involved in eating, drinking, irritability, aggression, and copulation in rats.

Investigated in 3 experiments with male hooded rats (N = 61) the effects of parasagittal cuts placed at 3 anterior-posterior positions. Cuts that separated portions of the medial from the lateral hypothalamus produced severe hyposexuality if they lay lateral to the medial preoptic-anterior hypothalamic continuum. Hyperphagia, irritability, and modest sexual impairment were produced if the cuts lay lateral to the anterior tips of the ventromedial hypothalamic nuclei and slightly invaded the anterior hypothalamus. Posterior, but not anterior, medial-forebrain-bundle (MFB) cuts disrupted copulation. Central gray cuts resulted in slight hyperphagia, and reticular formation cuts resulted in hyposexuality. It is concluded that the medial hypothalamic nuclei exert their effects on eating, irritability, and copulation through their lateral connections with the lateral hypothalamus and those components of the MFB that descend on (or ascend from) the lower brainstem. (40 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hyperphagia and obesity produced by parasagittal and coronal hypothalamic knife cuts: Further evidence for a longitudinal feeding inhibitory pathway.

Hyperphagia and obesity are produced by parasagittal knife cuts through the medial hypothalamus and by coronal knife cuts through the posterior hypothalamus. Results of the present series of experiments with 91 female CFE rats indicate that the 2 types of cuts produce their overeating effect by severing the same neural pathway. Exp I demonstrated that unilateral parasagittal knife cuts combined with contralateral coronal cuts in either the posterior hypothalamus or the midbrain significantly increased food intake and body weight. Exp II revealed that bilateral parasagittal cuts and bilateral coronal cuts in the hypothalamus produced qualitatively similar effects on food intake, diurnal ingestive pattern, finickiness, and amphetamine anorexia. The 2 types of cuts differentially altered water intake, however. In Exp III, coronal cuts in the posterior hypothalamus, like parasagittal cuts in the medial hypothalamus, increased the food intake and body weight of Ss previously given bilateral parasagittal transections through the lateral perifornical region. The neuroanatomy and neurochemistry of the longitudinal feeding inhibitory pathway suggested by these results are discussed. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Atropine fails to block the overconsumption of sugar solutions by hypothalamic hyperphagic rats.

Adult female Sprague-Dawley rats given bilateral parasagittal knife cuts in the medial hypothalamus (VMH group) were hyperphagic and became obese on a chow diet, compared with sham-operated controls. VMH Ss also overconsumed, relative to controls, sucrose and glucose solutions during 30-min/day tests. Pretreating VMH and control Ss with atropine methyl nitrate (1.0, 5.0, or 10.0 mg/kg) reduced their intake of the sugar solutions in 3 of 5 experiments, and in all experiments it suppressed their 24-hr chow intake. However, VMH Ss continued to drink more of the sugar solutions than the controls after all atropine treatments, and in 3 of 4 experiments their hyperphagia on the chow diet was not blocked by the atropine. Results do not support the hypothesis that vagally stimulated insulin release or other cholinergically mediated cephalic responses of digestion are essential for the expression of hypothalamic hyperphagia and finickiness. (44 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Ingestive responses to homeostatic challenges in rats with ablations of the anterolateral neocortex.

Because rats with either anterolateral neocortical (AN) or lateral hypothalamic (LH) damage initially display similar feeding and drinking deficits and recovery patterns, the present study examined the possibility that anterolateral neocortical ablations would also produce similar chronic ingestive impairments to glucoprivic and hydrational challenges. 73 male Sprague-Dawley rats received AN or dorsoposterior neocortical lesions or served as unoperated controls. Ss with AN ablations exhibited normal feeding responses to food deprivation and glucoprivation induced by insulin (4–26 U/kg, sc) or 2-deoxydextroglucose (2-DG [125 or 250 mg/kg, ip]), but their response to 500 mg/kg or 2-DG was impaired. These Ss also drank normally in response to hypertonic saline injections and following water deprivation but only if food was available during the test session. Results indicate that, although the anterolateral neocortex and LH are anatomically related, these brain regions appear to be functionally dissimilar in terms of the regulation of ingestion. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Forebrain lesions differentially affect drinking elicited by dipsogenic challenges and injections of muscimol into the median raphe nucleus.

Injections of muscimol into the median raphe nucleus (MR) elicit intense drinking in normally hydrated rats. To determine whether this response is dependent on forebrain systems mediating other aspects of water intake, the authors examined the effects of lesions of the subfornical organ (SFO), median preoptic nucleus (MnPO), lateral preoptic area (LPO), or lateral hypothalamus (LH) on the drinking. Lesions of the SFO or LH attenuated muscimol-elicited drinking, whereas lesions of the MnPO or LPO increased water intake after the treatment. All of the lesion groups showed a deficit in drinking to injections of polyethylene glycol and at least one of the doses of hypertonic saline. Only the SFO- and LH-lesioned groups showed a suppression of drinking to systemic injections of angiotensin II, suggesting that the drinking elicited by intra-MR injections of muscimol may involve changes in the central circuits mediating angiotensin-induced drinking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Paraventricular hypothalamic lesions and medial hypothalamic knife cuts produce similar hyperphagia syndromes.

Compared the hyperphagia/obesity syndrome produced by paraventricular hypothalamic (PVH) lesions and that produced by medial hypothalamic (MH) knife cuts in adult female Sprague-Dawley rats. Each treatment produced hyperphagia and overweight on a chow diet, although the PVH effect was less than the knife cut effect. Each treatment also produced qualitatively similar ingestive responses to unpalatable quinine- and sucrose octaacetate-adulterated diets and to palatable dextrose and fat diets during the dynamic and static weight-gain phases. The PVH lesions and MH cuts disrupted day/night feeding patterns and elevated water intakes but not water/food intake ratios. However, PVH lesions, unlike MH cuts, did not increase emotional reactivity. The relation of the PVH syndrome to the classic hypothalamic hyperphagia syndrome is discussed. Also considered is the neuroanatomical substrate responsible for the PVH hyperphagic effect. (66 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lateral hypothalamic syndrome in rats: a comparison of the behavioral and neurochemical effects of lesions placed in the lateral hypothalamus and nigrostriatal bundle

The effects of total (T-NSB) and subtotal (S-NSB) destruction of the nigrostriatal bundle were compared with the effects of large lateral hypothalamic (LH) lesions on various aspects of the lateral hypothalamic syndrome. The T-NSB and LH lesions produced equivalent decreases in caudate and telencephalic contents of dopamine and norepinephrine, while with the exception of telencephalic dopamine, S-NSB lesions had consistently smaller effect. The T-NSB and LH lesions produced equivalent effects on duration of aphagia and adipsia (Stages 1 to 3) and on long-term decreases in body weight and ad lib water consumption, and these effects were always greater than those produced by the S-NSB lesion. These aspects of the lateral hypothalamic syndrome appeared to be related to the interruption of the nigrostriatal bundle and consequent decrease in caudate dopamine. The T-NSB and S-NSB lesions produced equivalent long-term deficits in water regulation as measured by drinking in the absence of food or in response to intra- and extracellular dehydration, but these deficits were always significantly less than those produced by the LH lesion. It was concluded that these regulatory deficits were not related to destruction of catecholamine pathways. All three lesions totally blocked eating in response to a glucoprivic challenge. This aspect of the lateral hypothalamic syndrome, therefore, results from destruction of a small portion of the lateral diencephalon and may be related to the interruption of the dopaminergic mesolimbic system.     

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)     

Vagotomy blocks hypothalamic hyperphagia in rats on a chow diet and sucrose solution, but not on a palatable mixed diet.

Adult female Sprague-Dawley rats were given ventromedial hypothalamic parasagittal knife cuts (VMH treatment) or control surgery (Con treatment), followed 10 days later by subdiaphragmatic vagotomy (Vag treatment) or sham vagotomy (Sham treatment). The hyperphagia and obesity produced by the VMH cuts to Ss on a chow diet was completely blocked by vagotomy (VMH-Vag group). Vag also inhibited the VMH Ss' overconsumption of a 20% sucrose solution during 1-hr/day and 24-hr/day tests, which contrasts with the effects of atropine treatment. However, when offered a selection of palatable foods (cookies, sweet milk, high-fat ration) in addition to chow, VMH-Vag Ss overate and gained considerably more weight than did the Con-Vag or the Con-Sham Ss. Con-Vag Ss, on the other hand, gained less weight than Con-Sham Ss on the palatable diet. Results indicate that intact subdiaphragmatic vagi are not essential for the expression of VMH hyperphagia and finickiness, and they therefore question the role of vagally mediated cephalic responses in the hypothalamic hyperphagia syndrome. On the other hand, results indicate that in brain-intact animals Vag suppresses the development of diet-induced obesity. (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Circadian rhythms and partial recovery of regulatory drinking in rats after lateral hypothalamic lesions.

Eight sighted male albino rats that had recovered spontaneous ingestive behavior after lesions of the lateral hypothalamus were challenged with acute injections of hypertonic NaCl administered at different times during the day-night cycle. Nine intact controls were also studied. Following these injections, drinking was observed only during the nighttime. After morning injections Ss frequently waited until nightfall before drinking, whereas Ss injected at night showed much shorter delays in the behavioral response; a similar nocturnal predominance of drinking was seen after food deprivation and in the ad-lib situation. Studies in 6 blind lesioned Ss suggest that these effects were due to an endogenous circadian rhythm. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of amphetamine and food deprivation on self-stimulation of the lateral hypothalamus and medial frontal cortex.

Intracranial self-stimulation of the lateral hypothalamus in 5 male Sprague-Dawley rats was markedly increased by subcutaneous dextroamphetamine administration and by food deprivation. In contrast, similar self-stimulation response rates obtained in the same Ss from the medial frontal cortex were unaffected by food deprivation and only slightly increased by dextroamphetamine administration. Furthermore, a large difference between dextro- vs levoamphetamine on response rate was obtained for lateral hypothalamic but not for medial frontal cortex self-stimulation. Results are consistent with a noradrenergic self-stimulation system for the lateral hypothalamus. Medial frontal cortex self-stimulation, however, appears to be mediated by a neuroanatomical and neurochemical system different from that of the lateral hypothalamus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Destruction of the medial forebrain bundle caudal to the site of stimulation reduces rewarding efficacy but destruction rostrally does not.

Rats with an electrode in the medial forebrain bundle (MFB) in or near the ventral tegmental area and another at the level of the rostral hypothalamus sustained large electrolytic lesions at either the rostral or the caudal electrode. The rewarding efficacy of stimulation through the other electrode was determined before and after the lesion. Massive damage to the MFB in the rostral lateral hypothalamus (LH) generally had little effect on the rewarding efficacy of more caudal stimulation, whereas large lesions in the caudal MFB generally reduced the rewarding efficacy of LH stimulation by 35–60%. Similar reductions were produced by knife cuts in the caudal MFB. These results appear to be inconsistent with the hypothesis that the reward fibers consist either of descending or ascending fibers coursing in or near the MFB. It is suggested that the reward fibers are collaterals from neurons with both their somata and their behaviorally significant terminals located primarily in the midbrain. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Feeding behavior in the rat with isolated medial hypothalamus

After complete, unilateral, frontolateral, dorsal isolation of the medial hypothalamus, VMH included, or fornix section above the hypothalamus, total food consumption and diurnal pattern of food intake were followed 85 days postoperatively. It is suggested that the saftety signals are generated not only in VMH nucleus, but in a VMH-retrochiasmatic region located anteriorly to the VMH.     

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)     

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)     

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.     

Interferon modulates glucose-sensitive neurons in the hypothalamus

Interferon-alpha (IFN) therapy induces feeding suppression that resembles anorexia. The hypothalamic glucose-sensitive neurons engage in feeding behavior. Coronal sections of rat brains, containing both the lateral hypothalamus (LH) and the ventromedial hypothalamus (VMH), as well as single-cell recordings were used to study the interaction between IFN and glucose-sensitive neurons. IFN suppressed the majority (78%) of LH neurons, while reduction in glucose concentration elicited excitation in the majority (85%) of the same neurons. The opposite effects were observed in the VMH, where IFN excited the majority of neurons (61%), and reduction in glucose concentration exerted the opposite effects in 64% of VMH recordings. Concomitant IFN and glucose reduction exhibited only the effects elicited by IFN, regardless of whether the glucose reduction caused excitation (LH) or suppression (VMH). This observation suggests that IFN causes anorexia by modulating the LH and VMH glucose-sensitive neurons.     

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)