Reactivity of normal and VMH-lesion rats to quinine-adulterated foods: Negative evidence for negative finickiness.

Conducted 2 experiments with ventromedial hypothalamic (VMH) and normal rats to examine (1) whether the anorexic properties of quinine depend on quinine's sensory properties or on its postingestive effects, and (2) whether VMH rats overrespond to quinine adulteration. These issues were examined by comparing the feeding adjustments to quinine by VMH and normal male Long-Evans rats in a sham-feeding situation and under normal feeding circumstances, on Ss' initial exposure to this drug. In Exp I, 17 Ss received VMH lesions or sham lesions before being sham fed with various concentrations of quinine. In Exp II, 18 lesioned or sham-lesioned Ss were fed unadulterated food for 12 days, followed by a meal adulterated with quinine, 2 days of pure mash, and 1 day of quinine. Quinine caused significant depression of food intake in Ss. Little evidence exists for a conclusion that VMH rats are more reactive than normals to quinine-adulterated foods. Results suggest that major food intake perturbations of VMH rats are in response to hedonically positive dietary manipulations. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of quinine adulteration upon body weight of LH-lesioned and intact male rats.

Performed lateral hypothalamic (LH) lesions in 23 male Holtzman albino rats, resulting in a decline to 90% body weight (BW) compared to 14 controls. Thereafter, throughout a 9-wk observation period, BW was maintained at this chronically reduced level. Quinine adulteration of the diet resulted in an additional 12.8% decline in the level of maintained BW. Intact Ss fed the same quinine-adulterated diet likewise reduced and maintained BW at levels 12.3% below other controls fed an unadulterated diet. It is concluded that LH-lesioned male rats are not dependent upon the sensory qualities of an adlib diet to a degree differing from intact animals. Rather, they differ primarily in that they are attempting to defend a lower maintenance level or "set point" for BW. (15 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The abnormal quinine drinking aversion in the Brattleboro rat with diabetes insipidus is reversed by the vasopressin agonist DDAVP: a possible role for vasopressin in the motivation to drink

The Brattleboro rat with hypothalamic diabetes insipidus (BDI) has an abnormal aversion to drinking quinine-adulterated water compared with normal rats of the parent Long Evans (LE) strain. This BDI animal tolerates marked hypovolemia and decreased body weight in preference to drinking the quinine-adulterated fluid, indicative of a reduced motivation to drink. Acute or chronic treatment of BDI rats with desamino-8D arginine vasopressin (DDAVP) restored to normal their drinking response to quinine solution. Partial restoration of fluid turnover in BDI rats with hydrochlorothiazide, which has an antidiuretic effect in diabetes insipidus (when vasopressin is absent), failed to abolish the abnormal drinking response to quinine-adulterated solution in 8 out of 12 animals. In contrast, induction of diabetes mellitus in LE rats, which resulted in a marked polydipsia and polyuria even though vasopressin was still present, did not impair the drinking response to quinine solutions. These results suggest that the abnormal drinking response to quinine-adulterated fluid in BDI rats is reversed by treatment with the vasopressin V2-receptor agonist DDAVP but is unlikely to be a consequence of the restoration of fluid turnover to normal levels by a renal action. A possible central action involving vasopressin and the motivation to drink is discussed.     

Chonically reduced body weight in rats sustaining lesions of the lateral hypothalamus and maintained on palatable diets and drinking solutions.

12 male Holtzman rats sustaining lateral hypothalamic (LH) lesions regulated their body weight at a reduced level when maintained for 1 mo postlesion upon a wet mash diet. Thereafter, for a period of 84 days, half of these Ss were offered a high fat diet, whereas the remaining Ss continued to receive wet mash. A series of palatable drinking solutions were also offered. Body weight remained at reduced levels relative to 8 intake controls regardless of the diet offered, even under conditions of high fluid intake generated by the palatable drinking solutions. Results contradict the interpretation of E. J. Mufson and R. S. Wampler (see record 1973-00428-001) that the lower body weight observed in LH-lesioned animals is secondary to lesion-produced "finickiness" and/or dehydration resulting from hypodipsia. Rather, a primary shift in the set point for body weight appears to underlie the reduced levels of weight maintenance in LH-lesioned animals. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of ovarian and hypothalamic obesity syndromes in the female rat: Effects of diet palability on food intake and body weight.

Results of 2 experiments with 96 CFE female rats show that both ovariectomy and hypothalamic knife cuts produced hyperphagia and obesity in Ss. The ovarian obesity, however, unlike hypothalamic obesity, was virtually independent of diet palatability. Ovariectomized Ss became obese on quinine-adulterated diets which completely blocked hypothalamic obesity, and they displayed little further weight gain when given a high-fat diet which greatly potentiated hypothalamic obesity. Ovarian and hypothalamic obesity were also found to be additive irrespective of diet condition when both surgical treatments were combined in the same S; that is, ovariectomy increased the food intake and body weight of knife-cut Ss given the quinine or high-fat diet. In contrast to their dissimilar feeding effects, ovariectomy, hypothalamic cuts, and the combined surgeries did not differentially alter the aversion to a 0.01% quinine solution. Results indicate that ovarian obesity and hypothalamic obesity represent 2 different feeding disorders and are mediated by separate neural mechanisms. The functional nature of these disorders is discussed in light of recent body weight set point interpretations. (40 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Motivational and neuroanatomical specificity of hypodipsia for aversive solutions produced by medial preoptic injury to the rat.

In an experiment with a total of 28 Sprague-Dawley rats, bilateral medial preoptic lesions dramatically lowered the rejection threshold for quinine-adulterated water but not for food in 24-hr forced-choice tests. The detection threshold for quinine in a 2-bottle choice test, however, was unaffected by the medial preoptic lesion. Bilateral septal and lateral preoptic lesions had no effect on any quinine adulteration tests. The enhanced rejection of quinine-adulterated water in a forced-choice test by medial-preoptic-damaged Ss was also observed after 24 hrs of water deprivation. The plasma osmolality of medial preoptic Ss was significantly elevated above controls after 24 hrs of water deprivation. Findings suggest that a medial preoptic lesion produces a deficit in thirst-motivated behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preweanling rats: recovery from lateral hypothalamic damage

Preweanling male and female albino rats sustained lateral hypothalamic area (LHA) destruction at 10 days of age. Pups with bilateral LHA destruction (Bi-LHA) displayed the lateral hypothalamic recovery syndrome (LHRS) and recovered voluntary feeding and drinking between 44-75 days of age. The Bi-LHA rats of both sexes showed permanent deficits (through 200-275 days of age) in responding to hydrational challenges and did not feed in response to 2-deoxy-D-glucose treatment. Male Bi-LHA rats' body weights were permanently depressed by 20%-25%, whereas female body weight depression was only temporary. Rats sustaining LHA destruction on one side of the brain (Uni-LHA) displayed an abbreviated LHRS, recovering voluntary feeding and drinking by 25-32 days of age. The Uni-LHA rats showed some permanent deficits in responding to hydrational challenges, yet they displayed the same sex differential for body weight regulation as the Bi-LHA rats. The results of this investigation demonstrate nearly identical effects of LHA destruction whether sustained preweaning, postweaning, or during adulthood.     

Effect of a quinine-adulterated diet upon body weight maintenance in male rats with ventromedial hypothalamic lesions.

Reports results of 3 experiments with a total of 100 male Sprague-Dawley rats. Ss offered a quinine-adulterated diet after receiving either ventromedial hypothalamic or sham lesions displayed nearly identical periods of anorexia before maintaining their body weight at a stable but reduced level. When starved prior to surgery to a body weight below this reduced maintenance level, both ventromedial hypothalamic and control Ss displayed an initial period of rapid weight gain on the quinine-adulterated diet. When subsequently offered only this diet for an 8-wk period, both groups, after castration, maintained the same reduced level of body weight. It is concluded that ventromedial hypothalamic animals overeat and become obese on palatable diets but defend the same lower weight level as controls when challenged with unpalatable diets. Impairment of a mechanism setting the upper, but not the lower, weight limit is suggested to be responsible for the greatly expanded range of body weights generated in the ventromedial hypothalamic animal by manipulation of diet palatability. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

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.     

Influences of deviations of thyroid functions on the effects of MAOI in rats--changes of 5-HT, 5-HIAA and norepinephrine contents and tyramine uptake by the brain and fluctuation of the rectal temperature]

The drug 6-hydroxydopamine (6-OHDA) has been reported to reduce hypothalamic norepinephrine (NE) content after administration into the lateral ventricle without altering the dopamine content of tubero-infundibular neurons. Serum prolactin levels in male rats injected with 2 X 250 mug 6-OHDA were significantly higher than in untreated control rats. Intraventricular injection of male rats with artificial cerebrospinal fluid resulted in elevated mean prolactin levels similar to those observed in 6-OHDA-treated animals. Further experimentation on animals decapitated at different times after removal from the animal quarters, indicates that prolcatin levels in 6-OHDA-treated rats are continuously elevated whereas they rise from basal levels to extremely high levels in CSF-treated rats, thus resulting in similar mean values. The CSF-treated controls ate hypersensitive to the stress of being removed from their normal environment. Such an effect was not observed in 6-OHDA-treated nor in untreated, and thus stress-inexperienced rats. In a long term study, serum prolactin and luteinizing hormone (LH) levels were followed over a period of 71 days after 6-OHDA treatment. Prolactin levels increased within one day after treatment and stayed at a high level for 15 days. Subnormal prolactin values were measured 37 days after 6-OHDA treatment. Serum LH levels were below normal 3 h and one day and were increased 37 and 71 days after 6-OHDA treatment. These results suggest that NE is important in the transmission of stressful stimuli to hypothalamic prolactin regulating centers. They further suggest functional recovery of LH and prolactin regulating mechanisms after 6-OHDA treatment.     

Gastric pathology and aphagia following lateral hypothalamic lesions in rats: Effects of preoperative weight reduction.

Conducted 2 experiments with a total of 105 male albino rats. In Exp I, body weights of Ss were reduced gradually to 80% of normal weight by restricting food intake (dieting), and then Ss were given lateral hypothalamic (LH) lesions. Compared with Ss of normal body weight sustaining similar brain lesions, the dieted group displayed a shorter period of postoperative aphagia and less gastric pathology. In Exp II, a group of Ss was reduced to 80% of normal body weight by withholding all food (fasting) and then given LH lesions. Compared with dieted Ss sustaining similar brain damage, the fasted group displayed a longer period of postoperative aphagia and greater gastric pathology. Since the duration of aphagia could be shortened or lengthened by simple manipulations of preoperative body weight, the adequacy of sensorimotor or motivational hypotheses to account for aphagia is questioned. Results are more consistent with the suggestion that gastric abnormalities produced by LH lesions inhibit eating. (60 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Central administration of antisense oligodeoxynucleotides to neuropeptide Y (NPY) mRNA reveals the critical role of newly synthesized NPY in regulation of LHRH release

Compelling evidence shows that the episodic and cyclic secretion of hypothalamic luteinizing hormone releasing hormone (LHRH), the primary stimulator of pituitary LH release, is subject to regulation by neuropeptide Y (NPY). We have reported earlier that sequential treatment of ovariectomized (ovx) rats with estrogen and progesterone to stimulate a preovulatory-type LH surge elevated the levels of both NPY and preproNPY mRNA levels in the hypothalamus concomitant with dynamic changes in LHRH activity. The present study was designed to determine whether these elevations in NPY content and gene expression represent new synthesis of NPY that is crucial to elicit LHRH discharge. Ovx, steroid-primed rats received intracerebroventricular injections of an unmodified 20-mer oligodeoxynucleotide (oligo) complementary to the NPY mRNA sequence. Control rats were injected similarly with either saline or the sense or missense oligos. Results showed that control rats displayed a characteristic surge-type elevation in plasma LH levels that was not affected by the administration of missense or sense oligos. However, in rats injected with the antisense oligo, the steroid-induced LH surge was completely blocked. In an additional experiment, NPY peptide levels were measured in microdissected hypothalamic sites following the injection of antisense or missense oligos. NPY antisense oligo administration blocked the significant increases in NPY levels in the median eminence-arcuate area, the medial preoptic area and lateral preoptic area seen in control rats. These results suggest that sequential ovarian steroid treatment augments NPY synthesis in the hypothalamus and this newly synthesized NPY is critical for induction of the LHRH and LH surge.     

Syndrome X-like alterations in adult female rats due to neonatal insulin treatment

Hypothalamic structures are decisively involved in the regulation of body weight and metabolism. In syndrome X, complex metabolic alterations are present, which in women are found to be associated with disturbances of reproductive function and altered androgen levels. In previous experiments in rats, it was shown that a temporary intrahypothalamic hyperinsulinism during early life predisposes to overweight and diabetogenic disturbances later in life, associated with disorganization of hypothalamic regulatory centers. To investigate the possible long-term consequences of elevated peripheral insulin levels during ontogenesis, the following experiment was performed. Newborn female Wistar rats were treated during neonatal life with daily subcutaneous injections of long-acting insulin ([IRI group] 0.3 IU on days 8 and 9 of life and 0.1 IU on days 10 and 11 of life), whereas control animals (CO) received daily NaCl injections. This temporary exposure to increased insulin levels during a critical developmental period resulted in an increased body weight gain including juvenile life and adulthood (P < .01), accompanied by hyperinsulinemia (P < .01), impaired glucose tolerance (P < .05), and increased systolic blood pressure in adulthood (P < .025). No significant alterations were detected either in cyclicity and fertility or in the levels of testosterone, androstenedione, or dehydroepiandrosterone (DHEA) in IRI rats. Morphometric evaluation of hypothalamic nuclei showed a reduced numerical density of neurons (P < .025) and a decreased neuronal volume density (P < .025) within the ventromedial hypothalamic nucleus (VMN) of the IRI rats, whereas the antagonistic lateral hypothalamic area (LHA) was morphometrically unchanged. Newborn offspring of IRI rats (F1 generation) were overweight (P < .05) and had an increased pancreatic insulin concentration (P < .02). In conclusion, perinatal hyperinsulinism seems to predispose to the later development of syndrome X-like changes in female rats, possibly due to impaired organization of hypothalamic regulators of body weight and metabolism.     

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)     

Body weight and gastric acid secretion in rats with subdiaphragmatic vagotomy and lateral hypothalamic lesions.

Investigated the role of the vagus in the lateral hypothalamic (LH) syndrome to body weight loss in 80 male Sprague-Dawley albino rats. Ss were divided into 4 groups: (a) Ss with bilateral LH lesions that were subsequently given a bilateral subdiaphragmatic vagotomy, (b) LH Ss that received a control vagotomy operation, (c) nonlesion Ss that were given a subdiaphragmatic vagotomy, and (d) nonlesion Ss that received a control vagotomy operation. Both LH lesions and vagotomy reduced body weight levels, though the effects differed in terms of the length of time required to reach initial maximal loss, the time required to reach chronic levels of maintenance, and the severity of body weight reduction. Fasting gastric acid secretion was lowered by LH lesions, and the extent of this reduction was positively correlated with the reduction in body weight. Gastric contents after a 24-hr fast were greater in vagotomized than in nonvagotomized Ss. These data are discussed in relation to the role of the vagus in maintaining body weight levels and in relation to the changes in gastric functioning after LH lesions and vagotomy. (42 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Parotid gland tissue is able partially to assume pituitary functions under the influence of hypothalamic factors: in vivo and in vitro studies

To test whether salivary tissue can secrete pituitary hormones, female Sprague-Dawley rats were hypophysectomized (hypox) and the following were transplanted to the sella turcica: parotid gland (group 3, n=33), adrenal gland (group 4, n=30), muscle (group 5, n=24). Group 2 (n=21) had the sella turcica filled with dentist's cement. In addition a group of rats (group 1, n=22) remained intact as controls. All groups were followed for 8 months. Daily vaginal smears showed normal cyclicity in controls and constant dioestrus in all hypox groups. Blood samples, taken once every 30 days before and after LHRH stimulation, showed significantly lower (P<0.001) plasma LH values in all hypox groups compared with controls. In group 3, a gradual and significant increase (P<0.05) was observed in the LH response to LHRH in parallel with a partial recovery of oestrous smears. No LH modification was observed in the other hypox groups. Plasma prolactin (PRL) levels were also very low in all hypox groups and were unaltered throughout the study. At the end of the experiments, half the animals were killed by decapitation and the hypothalamic-pituitary areas carefully dissected, homogenized and analysed for LH and PRL content. The remaining animals were perfused with 4% paraformaldehyde to obtain fixing of the whole body tissues. Hypothalamic and transplant areas were carefully dissected, frozen, cut and submitted to immunochemical procedures. LH content in the graft of group 3 animals was markedly (P<0.001) lower than in the control pituitary, but significantly higher (P<0.05) than in the other hypox groups. Immunochemistry showed LH and PRL positive cells in the graft of group 3 animals, whereas neither positive cells, nor LH content were observed in the parotid gland in situ. Experiments were completed with in vitro cultures of parotid glands in the presence or absence (controls) of synthetic hypothalamic hormones or rat hypothalamic extracts. After 1.5 weeks of culture, a significantly higher LH concentration (P<0.05) was observed in the wells treated with synthetic hypothalamic hormones (216+/-46 pg/ml vs 41+/-6 pg/ml in controls). When hypothalamic extracts were used, the LH levels increased more markedly (1834+/-190 pg/ml vs 36+/-6 pg/ml in controls) and those values were maintained during 3 weeks of culture. Immunostaining of these cultures showed a positive LH reaction in the epithelial cells found in the hypothalamic extract-treated wells. Both in vivo and in vitro studies confirm the transdifferentiation of parotid gland tissue to pituitary hormone-producing cells under hypothalamic influence.     

Effects of lateral hypothalamic lesions on food intake of rats during exposure to cold.

Two experiments investigated the feeding behavior of 41 male Sprague-Dawley rats with lateral hypothalamic (LH) lesions and 13 Ss with chemical lesions of central dopaminergic neurons. LH damage impaired both physiological and behavioral responses of Ss during exposure to a 5°C environment. The LH-lesioned Ss usually did not conserve heat in the cold as well as did controls (n?=?13), nor did they always increase their caloric intake to meet their energy needs. However, when given sucrose solution to drink instead of water, LH-lesioned Ss increased their ingestion of chow in response to cold exposure. It is likely that the elevated consumption of palatable fluid served to relieve dehydration and thereby removed its constraints on eating, thus permitting hyperphagia to occur. In contrast to these results, Ss with large dopamine-depleting brain lesions, produced by intraventricular 6-hydroxydopamine treatments, always increased food intake when exposed to cold stress and demonstrated no apparent problems in peripheral vasoconstriction. Thus, it is unlikely that striatal dopamine depletions account for either the impaired feeding response or the inadequate heat conservation of rats with lateral hypothalamic lesions during cold stress. (33 ref) (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)