Effects of adrenal steroid agonists on food intake and macronutrient selection.

These experiments tested the effects of subcutaneous (SC) and paraventricular nucleus (PVN) administration of the steroid receptor agonists, corticosterone (CORT), aldosterone (ALDO), RU28362, and dexamethasone (DEX), on food intake and macronutrient selection during the first h of the dark feeding period in the rat. Results indicate that CORT and the selective type II receptor agonist RU28362 specifically stimulate carbohydrate ingestion after SC or PVN administration, while DEX has no effect on feeding. This selective effect of SC CORT on carbohydrate ingestion is dose dependent, seen at doses ranging from 0.125 to 2.0 mg/kg. Moreover, the stimulatory effects of CORT and RU28362 on carbohydrate intake are observed in ADX rats but not in sham rats. This is in contrast to SC and PVN administration of the type I receptor agonist ALDO, which specifically enhances fat ingestion in both sham and ADX rats. These results, with both peripheral and central steroid administration, reveal selective effects of type I and type II receptor stimulation on fat and carbohydrate intake, respectively.     

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

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

Galanin in the PVN increases nutrient intake and changes peripheral hormone levels in the rat

In self-selection feeding paradigms, rats display differential patterns of nutrient (protein, carbohydrate or fat) intake. Factors known to influence this selection include brain peptides as well as circadian parameters. In this series of experiments we investigated the role of PVN galanin in nutrient intake during the early and late dark periods in the rat. Rats were allowed to select between three isocaloric diets enriched in protein, carbohydrate or fat. Following a 2-week adaptation period, the animals' 24-h intake was monitored for 4 weeks. Galanin was injected into the PVN and food intake was measured 1, 2 and 24 h post-injection. Galanin significantly increased the 1 h total food intake but it failed to increase the intake of any particular nutrient. Galanin had no effect 2 or 24 h post-injection. Analysis of the data grouped by preference based on the rats 24 h baseline selection patterns over the 4-week period revealed that galanin seem to increase the preferred nutrient. That is, galanin preferentially increased the intake of the carbohydrate- or fat-rich diet in animals with high (over 40% of the total food intake) 24-h baselines in this particular nutrient. Finally, analysis of the plasma hormone levels after paraventricular galanin administration revealed a significant increase in noradrenaline levels, a small reduction in plasma insulin with no effects on adrenaline, glucose or corticosterone. The data revealed that galanin in the PVN influences both food intake and metabolic functioning. PVN galanin significantly increases sympathetic outflow and seems to stimulate the intake of the individual rat's preferred macronutrient.     

Hypothalamic implants of dilute estradiol fail to reduce feeding in ovariectomized rats

To investigate further the site where estradiol (E(2)) inhibits food intake, we tested the effects on feeding of subcutaneous and intrahypothalamic implants of 10% E(2) benzoate in cholesterol (CHOL) or CHOL alone. E(2) was implanted subcutaneously in Silastic tubes, and intrahypothalamically via bilateral 29-gauge cannulas into the paraventricular nucleus (PVN) or the medial preoptic area (MPA) of ovariectomized (OVX) Sprague-Dawley and Long-Evans rats. Three-day implant periods followed 3-day baseline periods. Rats were allowed ad libitum access to chow and tap water, and food intake and body weight were measured each day. Subcutaneous 10% E(2) implants in Sprague-Dawley rats reduced food intake 21% on Day 2 and 34% on Day 3 (P's<.01) and decreased 3-day body weight gain 11 g (P<.05). In contrast, 10% E(2) implants in the PVN of Sprague-Dawley rats did not change food intake or body weight. Implants of 10% or 20% E(2) in the MPA also failed to decrease food intake. MPA implants of 10% E(2) decreased body weight gain 8 g (P<.05), but MPA implants of 20% E(2) decreased weight gain only 4 g (P>.05). To determine whether the strain of rat affected our negative results on food intake, we implanted 10% E(2) into the PVN of Long-Evans rats. Again, PVN E(2) did not decrease food intake significantly in comparison to the pretest baseline. PVN E(2) did, however, decrease body weight gain 5 g and decreased food intake 6% compared to rats with implants of CHOL (both P<.05), but these effects appeared to be due to an increase in feeding in the CHOL group in comparison to their baseline. Finally, CHOL and E(2) implants did not impair the responsivity of the PVN because acute implants of norepinephrine (NE) into the PVN of E(2)- or CHOL-treated Long-Evans rats significantly increased food intake. Our results do not support the hypothesis that E(2)'s actions in either the PVN or the MPA are sufficient to account for its inhibitory effects on feeding.     

Involvement of brain ketone bodies and the noradrenergic pathway in diabetic hyperphagia in rats

Uncontrolled type 1 diabetes leads to hyperphagia and severe ketosis. This study was conducted to test the hypothesis that ketone bodies act on the hindbrain as a starvation signal to induce diabetic hyperphagia. Injection of an inhibitor of monocarboxylate transporter 1, a ketone body transporter, into the fourth ventricle normalized the increase in food intake in streptozotocin (STZ)-induced diabetic rats. Blockade of catecholamine synthesis in the hypothalamic paraventricular nucleus (PVN) also restored food intake to normal levels in diabetic animals. On the other hand, hindbrain injection of the ketone body induced feeding, hyperglycemia, and fatty acid mobilization via increased sympathetic activity and also norepinephrine release in the PVN. This result provides evidence that hyperphagia in STZ-induced type 1 diabetes is signaled by a ketone body sensed in the hindbrain, and mediated by noradrenergic inputs to the PVN.     

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.     

Noradrenergic feeding elicited via the paraventricular nucleus is dependent upon circulating corticosterone

Feeding behavior elicited by injection of norepinephrine (NE) into the paraventricular nucleus (PVN) of satiated rats has been shown to be abolished by hypophysectomy. To determine the specific nature of this dependence of NE's action on pituitary hormones, the efficacy of PVN-injected NE was examined in rats subjected to hypophysectomy, as well as to adrenalectomy, thyroidectomy, and gonadectomy, and also in operated rats receiving hormone replacement therapy. The feeding response induced by NE was almost completely abolished in adrenalectomized as well as hypophysectomized animals, but remained unimpaired after thyroidectomy and gonadectomy. The NE response was significantly restored in hypophysectomized rats by daily subcutaneous injections of corticosterone, but not by thyroxine, testosterone, insulin, or the mineralocorticoid deoxycorticosterone. In adrenalectomized rats, subcutaneous corticosterone implants as well as daily corticosterone injections (as opposed to deoxycorticosterone injections) effectively restored the NE eating effect. Radioimmunoassay of plasma corticosterone indicated that the level of hormone was positively correlated with the strength of the animals' response to the NE injection. These findings demonstrate that the loss of response to NE subsequent to hypophysectomy is due to a disruption of the hypothalamo-pituitary-adrenal axis. The glucocorticoids of the adrenal gland appear to be the essential humoral factor interacting permissively with PVN-injected NE to elicit feeding.     

Noradrenaline-induced feeding responses in the rat do not depend on food characteristics

The noradrenergic system of the hypothalamic paraventricular nuclei (PVN) has been associated with feeding, but whether it controls feeding in a way that is relevant to energy balance is still unclear. Rats were maintained on a high energy, carbohydrate-rich diet (HC) or a low energy, carbohydrate-free, protein-rich diet (LP) until their daily energy intakes equalized. When injected with noradrenaline (NA) into the PVN, they ingested the same amounts of both diets so that the animals on the LP diet consumed only half the total energy of those on the HC diet. Continuous delivery of NA into the PVN via a microdialysis probe induced chewing on non-nutritive pieces of corks. The same chewing pattern could again be elicited by the subsequent NA deliveries. It is concluded that the nutritional value of a diet is irrelevant to the NA feeding response. The failure of NA administration to increase rat feeding in terms of energy intake, combined with its ability to stimulate chewing, suggests that the primary role of the NA system of the PVN may not be controlling the carbohydrate and energy intake, but rather gating behavioral responses that under appropriate circumstances may lead to ingestion.     

Food deprivation decreases vasopressin mRNA in the supraoptic and paraventricular nuclei of the hypothalamus in rats

We examined the effect of food deprivation for three days on hypothalamic arginine vasopressin (AVP) mRNA in rats. Simultaneously the effect of water deprivation for the same period was examined as a model of dehydration. Levels of AVP mRNA in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) were determined by semiquantitative in situ hybridization histochemistry. Water deprivation increased AVP mRNA in both nuclei as previously reported. In contrast, food deprivation decreased AVP mRNA in these nuclei. The changes in AVP mRNA levels in the PVN were observed in the magnocellular subdivision of the nucleus. Plasma levels of ACTH and corticosterone were greatly increased in both treated groups of rats. Plasma AVP and osmolality levels were significantly elevated in water-deprived rats but not in food-deprived rats. These observations indicated that both food deprivation and water deprivation stimulated the pituitary-adrenal axis and that a reduction in AVP mRNA levels in food-deprived rats was caused by food deprivation but not by glucocorticoid feedback suppression nor by altered plasma osmolality.     

Structure-function analysis of stimulation of food intake by neuropeptide Y: effects of receptor agonists.

Neuropeptide Y (NPY) is a potent natural orexigenic signal in the rat. In this study, we have compared the effects of several COOH-terminal fragments of NPY and NPY receptor agonists on cumulative food intake in male rats. Rats were implanted with permanent cannulae either into the third cerebroventricle or paraventricular nucleus (PVN). NPY1-36 and various COOH-terminal fragments of NPY, two agonist analogues [Leu31, Pro34]NPY and NPY 1-4-Aca (epsilon-amino-caproic acid)-25-36, were administered intracerebroventricularly (ICV) or directly into the PVN, and the cumulative 2-h food intake response was compared. We observed that peptides that were effective by ICV were also effective when administered into the PVN, but smaller amounts of the peptides were required after PVN injection to evoke an equivalent food intake response. Injection of NPY1-36 induced a dose-dependent increment in food intake. Surprisingly, deletion of NH2-terminal tyrosine residue did not adversely affect feeding behavior. In fact, NPY2-36 was consistently more effective than NPY1-36; the enhancement in feeding by NPY2-36 was dose-related and was higher than evoked by NPY1-36 at each dose tested. Further serial deletion of aminoacids at NH2-terminal resulted in complete loss of activity. In addition, NPY agonist analogue, NPY 1-4-Aca-25-36, failed to stimulate feeding. However, NPY Y1 receptor agonist, [Leu31, Pro34]NPY, but not Y2 receptor agonist, NPY13-36, stimulated feeding.(ABSTRACT TRUNCATED AT 250 WORDS)     

Induction of FOS expression by acute immobilization stress is reduced in locus coeruleus and medial amygdala of Wistar-Kyoto rats compared to Sprague-Dawley rats

Activation of the brain noradrenergic system during acute stress is thought to play an important integrative function in coping and stress adaptation by facilitating transmission in many brain regions involved in regulating behavioral and physiologic components of the stress response. Compared with outbred control Sprague-Dawley (SD) rats, inbred Wistar-Kyoto (WKY) rats exhibit an exaggerated hypothalamic-pituitary-adrenal (HPA) response as well as increased susceptibility to certain forms of stress-related pathology. However, we have also shown previously that WKY rats exhibit reduced anxiety-like behavioral reactivity to acute stress, associated with reduced activation of the brain noradrenergic system. Thus, to understand better the possible neurobiological mechanisms underlying dysregulation of the stress response in WKY rats, we investigated potential strain differences in stress-induced neuronal activation in brain regions that are both involved in regulating behavioral and neuroendocrine stress responses, and are related to the noradrenergic system, either as targets of noradrenergic modulation or as sources of afferent innervation of noradrenergic neurons. This was accomplished by visualizing stress-induced expression of Fos immunoreactivity in the paraventricular nucleus of the hypothalamus, lateral bed nucleus of the stria terminalis, central nucleus of the amygdala, and medial nucleus of the amygdala (MeA), as well as the noradrenergic nucleus locus coeruleus (LC). Stress-induced Fos expression was found to be decreased in the LC and MeA of WKY rats compared with similarly stressed SD rats, whereas no strain differences were observed in any of the other brain regions. This suggests that strain-related differences in activation of the MeA may be involved in the abnormal neuroendocrine and behavioral stress responses exhibited by WKY rats. Moreover, as the MeA is both an afferent as well as an efferent target of the brainstem noradrenergic system, reduced MeA activation may either be a source of reduced noradrenergic reactivity seen in WKY rats, or possibly a consequence. Nonetheless, understanding the mechanisms underlying altered stress reactivity in models such as the WKY rat may contribute to a better understanding of stress-related psychopathologies such as depression, post-traumatic stress disorder or other anxiety disorders.     

Glucose-dependent changes in alpha 2-noradrenergic receptors in hypothalamic nuclei

Evidence indicates that hypothalamic norepinephrine (NE), acting via alpha 2-noradrenergic receptors, and also circulating glucose both have an important role in the control of normal feeding behavior in rats. In this report, we studied the relationship between glucose and the alpha 2-noradrenergic system, by manipulating blood glucose levels and analyzing changes in the binding of [3H]p-aminoclonidine [( 3H]PAC) to alpha 2-noradrenergic receptors in discrete hypothalamic areas. Brief periods (1-3 hr) of food deprivation, at the onset of the dark cycle, produced a significant decline in serum glucose levels and a simultaneous decrease in alpha 2-receptor binding sites, specifically in the hypothalamic paraventricular nucleus (PVN) as opposed to other hypothalamic areas. Restoration of circulating glucose levels, by refeeding for 0.5 hr after 2.5 hr food deprivation or by administration of glucose to 1 hr food-deprived rats, prevented this decline in serum glucose, as well as the reduction in PVN alpha 2-noradrenergic receptor density. In each of these experiments, a strong positive correlation between circulating glucose levels and PVN alpha 2-noradrenergic receptor sites was obtained. These findings suggest that blood glucose has direct impact upon alpha 2-noradrenergic receptor activity in the PVN and may affect feeding behavior, in part, through this neurochemical system.     

The suprachiasmatic nucleus participates in food entrainment: a lesion study

Daily feeding schedules entrain temporal patterns of behavior, metabolism, neuronal activity and clock gene expression in several brain areas and periphery while the suprachiasmatic nucleus (SCN), the biological clock, remains coupled to the light/dark cycle. Because bilateral lesions of the SCN do not abolish food entrained behavioral and hormonal rhythms it is suggested that food entrained and light entrained systems are independent of each other. Special circumstances indicate a possible interaction between the light and the food entrained systems and indicate modulation of SCN activity by restricted feeding. This study explores the influence of the SCN on food entrained rhythms. Food entrained temporal profiles of behavior, core temperature, corticosterone and glucose, as well as Fos and PER1 immunoreactivity in the hypothalamus and corticolimbic structures were explored in rats bearing bilateral SCN lesions (SCNX). In SCNX rats food anticipatory activity and the food entrained temperature and corticosterone increase were expressed with earlier onset and higher values than in intact controls. Glucose levels were lower in SCNX rats in all time points and SCNX rats anticipation to a meal induced higher c-Fos positive neurons in the hypothalamus, while a decreased c-Fos response was observed in corticolimbic structures. SCNX rats also exhibited an upregulation of the PER1 peak in hypothalamic structures, especially in the dorsomedial hypothalamic nucleus (DMH), while in some limbic structures PER1 rhythmicity was dampened. The present results indicate that the SCN participates actively during food entrainment modulating the response of hypothalamic and corticolimbic structures, resulting in an increased anticipatory response.     

Noradrenergic inputs to the paraventricular hypothalamus contribute to hypothalamic-pituitary-adrenal axis and central Fos activation in rats after acute systemic endotoxin exposure

Noradrenergic (NA) neurons within the nucleus of the solitary tract (NST) and caudal ventrolateral medulla (VLM) innervate the hypothalamic paraventricular nucleus (PVN) to initiate and modulate hypothalamic-pituitary-adrenal (HPA) axis responses to interoceptive stress. Systemic endotoxin (i.e. bacterial lipopolysaccharide, LPS) activates NA neurons within the NST and VLM that project to the PVN and other brain regions that receive interoceptive signals. The present study examined whether NA neurons with axonal inputs to the PVN are necessary for LPS to activate Fos expression within the PVN and other interoceptive-related brain regions, and to increase plasma corticosterone. Male Sprague-Dawley rats received bilateral stereotaxic microinjections of DSAP (saporin toxin conjugated to an antibody against dopamine-beta-hydroxylase, DbH) into the PVN to destroy NA inputs. Control rats were microinjected with vehicle into the PVN or received no PVN injections. Two weeks later, DSAP and control rats were injected i.p. with LPS (200 microg/kg BW) or saline vehicle, and perfused with fixative 2.5-3 h later. Brain tissue sections were processed to reveal nuclear Fos protein and cytoplasmic DbH immunolabeling. DSAP lesions depleted NA terminals in the PVN and bed nucleus of the stria terminalis, reduced the number of NA cell bodies in the NST and VLM, attenuated PVN Fos activation after LPS, and attenuated LPS-induced increases in plasma corticosterone. These findings support the view that NA projections from hindbrain to hypothalamus are necessary for a full HPA axis response to systemic immune challenge.     

The effects of 5-HT1A and 5-HT2C receptor agonists on behavioral satiety sequence in rats

The present study examined the effects of 5-HT1A and 5-HT2C receptor agonists on behavioral satiety sequence (BSS) in rats. The 5-HT1A receptor agonist, 8-OH-DPAT (0.5 microg), and the 5-HT2C receptor agonist, Ro-60-0175 (3.0 microg), were injected into the paraventricular nucleus (PVN) of rats. The animals were maintained on an ad libitum feeding paradigm with access to water and individual sources of protein, carbohydrate, and fat. Intra-PVN administration of each agonist was associated with decreased carbohydrate consumption. The effect was enhanced by the administration of both agonists together. Behavioral analysis indicated that co-administration of 8-OH-DPAT and Ro-60-0175 interrupted the natural BSS with an increase in non-feeding behavior, whereas the 8-OH-DPAT alone promoted early development of the natural BSS. In conclusion, the 5-HT receptor agonists affected serotonergic modulation of feeding behavior in a functionally selective way.     

The rise, fall, and resurrection of the ventromedial hypothalamus in the regulation of feeding behavior and body weight

Early researchers found that lesions of the ventromedial hypothalamus (VMH) resulted in hyperphagia and obesity in a variety of species including humans, which led them to designate the VMH as the brain's "satiety center." Many researchers later dismissed a role for the VMH in feeding behavior when Gold claimed that lesions restricted to the VMH did not result in overeating and that obesity was observed only with lesions or knife cuts that extended beyond the borders of the VMH and damaged or severed the ventral noradrenergic bundle (VNAB) or paraventricular nucleus (PVN). However, anatomical studies done both before and after Gold's study did not replicate his results with lesions, and in nearly every published direct comparison of VMH lesions vs. PVN or VNAB lesions, the group with VMH lesions ate substantially more food and gained twice as much weight. Several other important differences have also been found between VMH and both PVN and VNAB lesion-induced obesity. Concerns regarding (a) motivation to work for food and (b) the effects of nonirritative lesions have also been addressed and answered in many studies. Lesion studies with weanling rats and adult pair-tube-fed rats, as well as recent studies of knockout mice deficient in the orphan nuclear receptor steroidogenic factor 1, indicate that VMH lesion-induced obesity is in large part a metabolic obesity (due to autonomic nervous system disorders) independent of hyperphagia. However, there is ample evidence that the VMH also plays a primary role in feeding behavior. Neuroimaging studies in humans have shown a marked increase in activity in the area of the VMH during feeding. The VMH has a large population of glucoresponsive neurons that dynamically respond to blood glucose levels and numerous histamine, dopamine, serotonin, and GABA neurons that respond to feeding-related stimuli. Recent studies have implicated melanocortins in the VMH regulation of feeding behavior: food intake decreases when arcuate nucleus pro-opiomelanocortin (POMC) neurons activate VMH brain-derived neurotrophic factor (BDNF) neurons. Moderate hyperphagia and obesity have also been observed in female rats with damage to the efferent projections from the posterodorsal amygdala to the VMH. Hypothalamic obesity can result from damage to either the POMC or BDNF neurons. The concept of hypothalamic feeding and satiety centers is outdated and unnecessary, and progress in understanding hypothalamic mechanisms of feeding behavior will be achieved only by appreciating the different types of neural and blood-borne information received by the various nuclei, and then attempting to determine how this information is integrated to obtain a balance between energy intake and energy output.     

下丘脑室旁核外源性orexin-A对肥胖大鼠摄食的影响及NPY受体信号的调控

目的:探讨饮食诱导肥胖(DIO)大鼠神经肽Y(NPY)受体信号通路是否参与下丘脑室旁核(PVN)外源性注射食欲素A(orexin-A)对摄食和葡萄糖敏感(GS)神经元兴奋性的调控。方法:采用荧光免疫组织化学实验观察PVN中orexin-A受体(即食欲素1型受体,OX1R)和NPY受体Y5(NPY-5R)的表达;采用单细胞外放电记录观察orexin-A对PVN内GS神经元兴奋性的影响;分别于SD大鼠和DIO大鼠PVN埋置套管,经套管注射orexinA、OX1R拮抗剂SB-334867和NPY-5R拮抗剂CGP-71683,观察大鼠0~2 h和0~4 h摄食量。结果:DIO大鼠PVN中OX1R和NPY-5R的表达显著高于SD大鼠。Orexin-A抑制PVN内葡萄糖抑制性(GI)神经元,兴奋葡萄糖兴奋性(GE)神经元,但是orexin-A对GS神经元的兴奋或抑制效应可被NPY-5R拮抗剂CGP-71683部分阻断,且与SD大鼠相比,orexin-A对DIO大鼠PVN内GS神经元兴奋或抑制效应更加明显。PVN内注射orexin-A可增加SD大鼠和DIO大鼠摄食量。但是orexin-A诱导的促摄食效应被NPY-5R拮抗剂CGP-71683部分阻断。与SD大鼠相比,orexin-A诱导的促摄食效应在DIO大鼠中更加明显。结论:PVN内外源性注射orexin-A可能主要通过OX1R信号通路参与大鼠摄食和GS神经元兴奋性调控,NPY-5R信号也参与了该过程调控,在DIO大鼠中更敏感。     

Responses of hypothalamic paraventricular neurons in vitro to norepinephrine and other feeding-relevant agents

To investigate paraventricular hypothalamic neuronal actions responsible for the effects of neurotransmitters on feeding, and to test the notion that a single population of cells there could account for feeding effects, hypothalamic slices containing the paraventricular nucleus (PVN) were prepared from rats. Electrophysiological responses of individual PVN neurons to feeding-inducing agents norepinephrine (NE) and gamma-aminobutyric acid (GABA), and to anorexic agents serotonin (5-HT) and histamine (Hist) were examined. NE inhibited neuronal activity through alpha 2-adrenergic receptors, and excited through alpha 1-receptors. alpha 2-receptors are known to mediate the behavioral effect of NE. NE inhibited most clearly those neurons that otherwise fired continuously in this type of in vitro preparation. GABA affected the activity of 37% of the neurons tested, primarily by inhibition. The inhibitory action of GABA can be related to its feeding-inducing effect. GABA in PVN can also attenuate excitatory responses and enhance inhibitory responses to NE or 5-HT. 5-HT caused excitatory and inhibitory responses with the former action outnumbering the latter by approximately 3 to 1. Since this would result in a net excitation, it appears that 5-HT in PVN inhibits feeding mainly by exciting neuronal activity. Hist excited 72% and inhibited only 2% of PVN neurons. The excitation was blocked by H1-antagonists, which have been shown to mediate Hist effect on feeding. Comparing across neurons, the inhibitory response to NE was correlated with that to GABA, but not with any responses to 5-HT or Hist. The excitatory responses to Hist correlated with 5-HT responses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Circadian rhythm of feeding induced changes in hypothalamic Met-enkephalin concentrations

Accumulating evidence suggests that opioid peptides play an important role in the hunger component of the control of food intake. The enkephalins, one of the opioid peptide families, stimulate feeding when injected into specific hypothalamic areas and endogenous concentrations change with the fed/fasted condition of rats and sheep and with phase of circadian cycle. To demonstrate a possible circadian rhythm in feeding-induced changes in Met-enkephalin (MEK), 54 male rats initially weighing 255 +/- 3 g were adapted to a 12-hr fast during the light (light-fasted) or dark (dark-fasted) phase of the circadian cycle, then sacrificed before (non-fed) or after (fed) being allowed to eat a meal. In non-fed compared with fed rats, MEK concentrations were higher in the paraventricular nucleus (PVN, 170 vs. 109 pg/mg tissue, p less than 0.05) and ventromedial hypothalamus (VMH, 209 vs. 161 pg/mg tissue, p less than 0.05) in the dark (light-fasted) but not light (dark-fasted), even though rats ate a larger meal in the light (8.6 vs. 5.0 g, p less than 0.01). In rats fed the same amount of food in the light (dark-fasted) as ad lib fed rats in the dark (light-fasted), MEK concentrations did not differ in the PVN or VMH, suggesting that circadian rhythm is more important than meal size. Rats gavaged with an amount of milk equal in calories to dark ad lib-fed rats (light-fasted) had MEK concentrations not different from light-fasted non-fed rats (216 vs. 209 pg/mg tissue, NS) suggesting that feeding behavior, pregastric stimuli and/or form of diet is important for influencing MEK concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)