Paraventricular noradrenergic systems participate in angiotensin II-induced drinking

The present study was designed to examine the role of noradrenergic systems in the hypothalamic paraventricular nucleus (PVN) in the drinking response induced by microinjection of angiotensin II (ANG II) into the subfornical organ (SFO) in the awake rat. Intracerebral microdialysis techniques were utilized to quantify the extracellular concentration of noradrenaline (NA) in the region of the PVN. Injections of ANG II (10⁻⁶ M, 0.2 μl) into the SFO significantly increased NA release in the PVN area. The increase in the NA concentration caused by the ANG II injection was significantly attenuated by water ingestion. In urethane-anesthetized rats, injections of ANG II into the SFO elicited an elevation in mean arterial pressure (MAP). On the other hand, intravenous injections of the -agonist metaraminol (5 μg) slightly decreased the release of NA in the PVN area that accompanied an elevation in MAP. These results show that the noradrenergic system in the PVN area may be involved in the dipsogenic response induced by ANG II acting at the SFO.     

Endorphinergic and alpha-noradrenergic systems in the paraventricular nucleus: effects on eating behavior

Brain cannulated rats were injected with the opioid peptide beta-endorphin (beta-EP) directly into the hypothalamic paraventricular nucleus (PVN) where norepinephrine (NE) is most effective in stimulating eating behavior. Beta-Endorphin (1.0 nmole) reliably increased food intake in satiated animals, and this response was blocked by local administration of the selective opiate antagonist naloxone. The eating induced by beta-EP was positively correlated in magnitude with the NE response and, like NE, was antagonized by PVN injection of the alpha-noradrenergic blocker phentolamine. Naloxone had no effect on NE-induced eating, and the dopaminergic blocker fluphenazine failed to alter either beta-EP or NE eating. When injected simultaneously, at maximally effective doses, beta-EP and NE produced an eating response which was significantly larger than either of the responses elicited separately by beta-EP or NE and was essentially equal to the sum of these two responses. The evidence obtained in this study suggests that beta-EP and NE stimulate food ingestion through their action on PVN opiate and alpha-noradrenergic receptors, respectively, and that beta-EP's action is closely related to, and in part may be dependent upon, the PVN alpha-noradrenergic system for feeding control.     

Insatiable feeding evoked in rats by recurrent perfusion of neuropeptide Y in the hypothalamus

Hyperphagic-like intake of food was determined in the unrestrained rat during the sustained elevation over time of neuropeptide Y (NPY) within the paraventricular nucleus (PVN) and surrounding hypothalamic regions. A single guide tube was implanted stereotaxically in each of 22 rats for localized, intermittent perfusions of a CSF vehicle, nondeprotected NPY(1-36) or native NPY. Each site in the PVN of the fully sated rat was perfused repeatedly over a 5.0-h interval by means of a standard push-pull cannula system at a rate of 20 microliters/min for 6.0 min in one of three concentrations: 0.2, 1.0 and 2.0 micrograms/min. Two perfusions of 1.0 micrograms/min NPY evoked an intake of 4.6 +/- 1.1 g of food over a 3.0-h period, whereas 4-7 and 8-15 perfusions of this concentration of NPY, distributed over 5.0 h, induced the sated rats to eat a total of 12.0 +/- 1.1 g and 33.2 +/- 3.0 g, respectively. During a fixed number of 10 hypothalamic perfusions distributed over 5.0 h, concentrations of 0.2 and 2.0 micrograms/min NPY caused a cumulative intake of food in the rats of 14.2 +/- 2.0 g and 31.7 +/- 3.3 g, respectively. Under each condition, parallel push-pull perfusions of either control solution in the same hypothalamic sites were without effect on feeding. During the 5.0-h interval of repeated perfusions, successive bouts of eating occurred with individual intakes of food reaching as high as 49.0 g, which exceeded by up to two-fold the entire daily consumption of food. However, ingestion of water was unaffected by perfusion of NPY.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stimulation of feeding by galanin: anatomical localization and behavioral specificity of this peptide's effects in the brain.

The neuropeptide galanin (GAL) has been found to elicit eating after injection into the hypothalamic paraventricular nucleus (PVN). To determine whether GAL's effect in the brain is anatomically specific, this peptide (0.1 or 0.3 nmol) was microinjected into one of 14 different brain areas of rats, and its impact on subsequent food intake was measured. Among the hypothalamic sites tested, only the PVN and the adjacent periventricular region yielded a significant eating response to GAL. With injection into the PVN, a feeding response was observed without apparent changes in other food-associated behaviors, e.g., drinking, grooming, resting and sleeping, or low and high levels of activity. All other hypothalamic and extrahypothalamic sites tested were unresponsive to GAL, with the exception of the amygdala where a significant eating response was observed. These findings suggest that central GAL elicits feeding by acting in an anatomically localized and behaviorally specific manner. In light of other pharmacological and anatomical evidence, it is suggested the PVN GAL, in modulating feeding behavior, may work in association with the catecholamine norepinephrine (NE) which is known to coexist with GAL in PVN neurons.     

Metabolic effects of galanin injections into the paraventricular nucleus of the hypothalamus.

The metabolic effects of single injections of galanin into the paraventricular nucleus of the hypothalamus (PVN) were investigated in an open-circuit calorimeter. Wistar rats were tested, with no food available during the tests. In the dose range of 0.03-0.3 nmol, galanin produced a very short-latency (approximately 2 minutes) and short-lasting (approximately 15 minutes) reduction in energy expenditure. Since the same doses had no effect on respiratory quotient or locomotor activity, the metabolic effect is not secondary to changes in energy substrate utilization or locomotor activity. This antithermogenic effect complements the eating stimulatory action of PVN galanin, and together these phenomena suggest a role for galanin as an anabolic neuropeptide. The similarity of galanin's effects to those of norepinephrine, with which it coexists in PVN nerve endings, further suggests the involvement of this amine and the PVN alpha2-noradrenergic system in galanin's mechanism of action.     

Ghrelin is an orexigenic and metabolic signaling peptide in the arcuate and paraventricular nuclei

Ghrelin is a 28-amino acid acylated peptide and is the endogenous ligand for the growth hormone secretagogue receptor (GHS-R). The GHS-R is expressed in hypothalamic nuclei, including the arcuate nucleus (Arc) where it is colocalized with neuropeptide Y (NPY) neurons. In the present study, we examined the effects of ghrelin on feeding and energy substrate utilization (respiratory quotient; RQ) following direct injections into either the arcuate or the paraventricular nucleus (PVN) of the hypothalamus. Ghrelin was administered at the beginning of the dark cycle at doses of 15-60 pmol to male and female rats. In feeding studies, food intake was measured 2 and 4 h postinjection. Separate groups of rats were injected with ghrelin, and the RQ (VCO(2)/VO(2)) was measured using an open circuit calorimeter over a 4-h period. Both Arc and PVN injections of ghrelin increased food intake in male and female rats. Ghrelin also increased RQ, reflecting a shift in energy substrate utilization in favor of carbohydrate oxidation. Because these effects are similar to those observed after PVN injection of NPY, we then assessed the impact of coinjecting ghrelin with NPY into the PVN. When rats were pretreated with very low doses of ghrelin (2.5-10 pmol), NPY's (50 pmol) effects on eating and RQ were potentiated. Overall, these data are in agreement with evidence suggesting that ghrelin functions as a gut-brain endocrine hormone implicated in the regulation of food intake and energy metabolism. Our findings are also consistent with a possible interactive role of hypothalamic ghrelin and NPY systems.     

Reduced feeding response to muscimol and neuropeptide Y in senescent F344 rats

Many mammals experience spontaneous declines in their food intake and body weight near the end of life, a stage we refer to as senescence. We have previously demonstrated that senescent rats have blunted food intake responses to intracerebroventricular injections of neuropeptide Y (NPY). In the present study, we tested the hypothesis that responsiveness to GABA, a putative potentiator of NPY's effect, is also diminished. Young and old male F344 rats received injections of NPY, muscimol, (MUS, a GABA-A receptor agonist), combinations of these two agents, and vehicle [artificial cerebrospinal fluid (aCSF)] into the hypothalamic paraventricular nucleus (PVN). Both young and old presenescent rats increased their food intake in response to NPY, MUS, and the combination of the two (in comparison to injections of aCSF). The combination treatment was generally more effective than either NPY or MUS alone. These data are consistent with suggestions that both NPY and GABA play a role in the regulation of feeding behavior. Senescent rats exhibited an attenuated NPY-induced food intake, no increase in response to MUS, and a response to NPY + MUS that was no larger than that of NPY alone. We conclude that PVN injections of GABA, as well as NPY, are less effective in stimulating feeding in senescent rats and suggest that alterations in their signaling pathways play a role in the involuntary feeding decrease seen near the end of life.     

Evidence for neuropeptide Y mediation of eating produced by food deprivation and for a variant of the Y1 receptor mediating this peptide's effect.

Neuropeptide Y (NPY) elicits eating when injected directly into the paraventricular nucleus (PVN) or perifornical hypothalamus (PFH). To identify the essential regions of the NPY molecule and the relative contributions of Y1 and Y2 receptors, the eating stimulatory potency of NPY was compared to that of its fragments, analogues, and agonists when injected into the PVN or PFH of satiated rats. Additionally, antisera to NPY was injected into the cerebral ventricles (ICV) to determine whether passive immunization suppresses the eating produced by mild food deprivation. Tests with NPY fragments revealed that NPY(2-36) was surprisingly potent, nearly three times more so than intact NPY. In contrast, fragments with further N-terminal deletions were progressively less effective or ineffective, as was the free acid form of NPY. Collectively, this suggests that both N- and C-terminal regions of NPY participate in the stimulation of eating. Tests with agonists revealed that the putative Y1 agonist [Pro34]NPY elicited a strong dose-dependent feeding response, while the putative Y2 agonist, C2-NPY, had only a small effect at the highest doses. Although this suggests mediation by Y1 receptors, the uncharacteristically high potency of NPY(2-36) may additionally suggest that the receptor subtype underlying feeding is distinct from that mediating other responses. Additional results revealed that ICV injection of antisera to NPY, which should inactivate endogenous NPY, produced a concentration-dependent suppression of eating induced by mild food deprivation. This finding, along with published work demonstrating enhanced levels of hypothalamic NPY in food-deprived rats, suggests that endogenous NPY mediates the eating produced by deprivation.     

Norepinephrine Microinjections in the Hypothalamic Paraventricular Nucleus Increase Extracellular Dopamine and Decrease Acetylcholine in the Nucleus Accumbens: Relevance to Feeding Reinforcement

Abstract: Norepinephrine (NE) was microinjected into the paraventricular nucleus (PVN), while microdialysis was used to monitor extracellular dopamine (DA) and acetylcholine (ACh) in the nucleus accumbens (NAc). The PVN is a site where exogenously administered NE can act through α₂ receptors to elicit eating behavior and preference for carbohydrates. It was hypothesized that NE in the PVN acts on a behavior reinforcement system by altering the DA/ACh balance in the NAc. NE microinjections (80 nmol in 0.3 µl), which effectively elicited feeding in satiated rats in a separate test, caused a significant increase in extracellular DA (109%) and decrease in ACh (−27%) when the same animals were tested in the absence of food. In contrast when the food was available and ingested, ACh increased (51%) instead of decreasing. These results support the hypothesis that a functional link exists between the PVN and the NAc in which DA helps initiate and ACh helps stop appetitive behavior involved in the reinforcement of eating.     

Brain pathways involved in the modulatory effects of noradrenaline in lateral septal area on cardiovascular responses

We have previously reported that stimulation of alpha-1 adrenoceptors by noradrenaline (NA) injected into the lateral septal area (LSA) of anaesthetized rats causes pressor and bradycardic responses that are mediated by acute vasopressin release into the circulation through activation of the paraventricular nucleus (PVN). Although the PVN is the final structure of this pathway, the LSA has no direct connections with the PVN, suggesting that other structures may connect these areas. To address this issue, the present study employed c-Fos immunohistochemistry to investigate changes caused by NA microinjection into the LSA in neuronal activation in brain structures related to systemic vasopressin release. NA microinjected in the LSA caused pressor and bradycardic responses, which were blocked by intraseptal administration of α-1 adrenoceptor antagonist (WB4101, 10?nmol/200?nL) or systemic V-1 receptor antagonist (dTyr(CH2)5(Me)AVP, 50?μg/kg). NA also increased c-Fos immunoreactivity in the prelimbic cortex (PL), infralimbic cortex (IL), dorsomedial periaqueductal gray (dmPAG), bed nucleus of the stria terminalis (BNST), PVN, and medial amygdala (MeA). No differences in the diagonal band of Broca, cingulate cortex, and dorsolateral periaqueductal gray (dlPAG) were found. Systemic administration of the vasopressin receptor antagonist dTyr AVP (CH2)5(Me) did not change the increase in c-Fos expression induced by intra-septal NA. This latter effect, however, was prevented by local injection of the alpha-1 adrenoceptor antagonist WB4101. These results suggest that areas such as the PL, IL, dmPAG, BNST, MeA, and PVN could be part of a circuit responsible for vasopressin release after activation of alpha-1 adrenoceptors in the LSA.     

PVN galanin increases fat storage and promotes obesity by causing muscle to utilize carbohydrate more than fat

To understand the function of the feeding-stimulatory peptide, galanin (GAL), in eating and body weight regulation, the present experiments tested the effects of both acute and chronic injections of this peptide into the paraventricular nucleus (PVN) of rats. With food absent during the test, acute injection of GAL (300 pmol/0.3 microl) significantly increased phosphofructokinase activity in muscle, suggesting enhanced capacity to metabolize carbohydrate, and reduced circulating glucose levels. It also decreased beta-hydroxyacyl-CoA dehydrogenase activity in muscle, indicating reduced fat oxidation, while increasing circulating non-esterified fatty acids (NEFA) and lipoprotein lipase activity in adipose tissue (aLPL). Chronic PVN injections of GAL (300 pmol/0.3 microl/injection) versus saline over 7-10 days significantly stimulated daily caloric intake and increased the weight of four dissected fat depots by 30-40%. These effects, accompanied by elevated levels of leptin, triglycerides, NEFA and aLPL activity, were evident only in rats on a diet with at least 35% fat. Thus, by favoring carbohydrate over fat metabolism in muscle and reversing hyperglycemia, PVN GAL may have a function in counteracting the metabolic disturbances induced by a high-fat diet. As a consequence of these actions, GAL can promote the partitioning of lipids away from oxidation in muscle towards storage in adipose tissue.     

Estradiol treatment increases feeding-induced c-Fos expression in the brains of ovariectomized rats

The steroid hormone estradiol decreases meal size by increasing the potency of negative-feedback signals involved in meal termination. We used c-Fos immunohistochemistry, a marker of neuronal activation, to investigate the hypothesis that estradiol modulates the processing of feeding-induced negative-feedback signals within the nucleus of the solitary tract (NTS), the first central relay of the neuronal network controlling food intake, and within other brain regions related to the control of food intake. Chow-fed, ovariectomized rats were injected subcutaneously with 10 microg 17-beta estradiol benzoate or sesame oil vehicle on 2 consecutive days. Forty-eight hours after the second injections, 0, 5, or 10 ml of a familiar sweet milk diet were presented for 20 min at dark onset. Rats were perfused 100 min later, and brain tissue was collected and processed for c-Fos-like immunoreactivity. Feeding increased the number of c-Fos-positive cells in the NTS, the paraventricular nucleus of the hypothalamus (PVN), and the central nucleus of the amygdala (CeA) in oil-treated rats. Estradiol treatment further increased this response in the caudal, subpostremal, and intermediate NTS, which process negative-feedback satiation signals, but not in the rostral NTS, which processes positive-feedback gustatory signals controlling meal size. Estradiol treatment also increased feeding-induced c-Fos in the PVN and CeA. These results indicate that modest amounts of food increase neuronal activity within brain regions implicated in the control of meal size in ovariectomized rats and that estradiol treatment selectively increases this activation. They also suggest that estradiol decreases meal size by increasing feeding-related neuronal activity in multiple regions of the distributed neural network controlling meal size.     

Naloxone inhibition of stress-induced daily torpor

$\text{Peromyscus maniculatus}$, deermice, were induced into daily torpor by restricting food to one-half daily ration. Intraperitoneal injection of naloxone (20 mg/kg) into mice habituated to daily IP injections of saline inhibited or modified the expression of daily torpor. In those individuals demonstrating long duration/ deep bouts (greater than 300 min/body temperature 20°C or below) naloxone administration resulted in 1) a significant decrease in the duration of torpor, 2) a significant elevation in minimum body temperatures attained during torpor and 3) a significant delay in the initiation time of torpor. In those individuals demonstrating short duration/shallow bouts (less than 300 min/ body temperatures above 20°C), naloxone administration resulted only in a significant delay of initiation time. Upon subsequent return to saline administration, however, these mice displayed a significant increase in the duration and depth of torpor. The results suggest that the endogenous opiates modulate the state of daily torpor.     

Regulation of Apoptosis in Nonapeptidergic Neurons of Rat Hypothalamus by Catecholamines in Experiments in vitro

Effects of noradrenaline (NA) and dopamine (DA) on apoptosis of nonapeptidergic neurons of supraoptic (SON) and paraventricular (PVN) nuclei of hypothalamus of male Wistar rats was studied in experiments in vitro. Incubation of hypothalamic sections in the medium with added NA was shown to induce an increase of the amount of pro-apoptotic protein caspase-9 in the nonapeptidergic neurons of the SON and PVN. A comparison of the level of neuronal NO-synthase with the level of caspase-9 expression in these neurons allows concluding that NA leads to initiation of apoptosis in neurons of the SON with mediation by nitric oxide (NO). In the PVN, the NA-induced initiation of apoptosis does not depend on the NO level. Addition of DA to the incubation medium results in an increase of the caspase-9 amount only in PVN neurons regardless of the NO content. The absence of neuronal death after the NA-induced increase of the caspase-9 level in the cells of SON and PVN seems to be due to increased expression of the anti-apoptotic protein bcl-2. Protection of the PVN neurons from death after addition of DA to the incubation medium is probably independent of the expression level of bcl-2. Thus, in the nonapeptidergic neurons of the SON and PVN, which are related by origin and by performed functions, modulation of the process of apoptosis by elevated concentrations of NA and DA is realized by different mechanisms.     

Neurotensin: effects of hypothalamic and intravenous injections on eating and drinking in rats

To investigate a role for the brain-gut peptide neurotensin (NT) in ingestive behavior, changes in food and water intake of food-deprived rats were examined following injection of NT into the paraventricular hypothalamic nucleus (PVN) or the mesenteric vein. Unilateral PVN NT (2.5, 5.0, 10.0 micrograms/0.3 microliter) produced substantial dose-dependent reductions in total food intake 0.5, 1, and 4 hr postinjection. In contrast, PVN NT had no effect on water intake and produced no change in grooming, rearing, sleeping, resting or locomotor activity. Bilateral PVN NT at a high dose (10.0 micrograms/side) suppressed consumption of solid or liquid diet in food-deprived rats, but did not affect water intake in water-deprived rats. This specificity is consistent with a role for CNS NT in feeding behavior. Intravenous NT (1-1000 pmole/kg/min for 30 min) did not specifically suppress food intake; however, low doses did increase water intake in food-deprived rats. These findings do not support a role for plasma NT in feeding, but do suggest that it may play a role in drinking behavior.     

Experimental dissociation of neural circuits underlying conditioned avoidance and hypophagic responses to lithium chloride

We previously reported that noradrenergic (NA) neurons in the nucleus of the solitary tract (NST) are necessary for exogenous CCK octapeptide to inhibit food intake in rats. To determine whether NST NA neurons also are necessary for lithium chloride (LiCl) to inhibit food intake and/or to support conditioned avoidance behavior, saporin toxin conjugated to an antibody against dopamine beta hydroxylase (DSAP) was microinjected bilaterally into the NST to ablate resident NA neurons. DSAP and sham control rats subsequently were tested for the ability of LiCl (0.15M, 2% body wt) to inhibit food intake and to support conditioned flavor avoidance (CFA). LiCl-induced hypophagia was significantly blunted in DSAP rats, and those with the most extensive loss of NST NA neurons demonstrated the most attenuated LiCl-induced hypophagia. Conversely, LiCl supported a robust CFA that was of similar magnitude in sham control and DSAP rats, including rats with the most extensive NA lesions. A terminal c-Fos study revealed intact LiCl-induced c-Fos expression in the lateral parabrachial nucleus and central amygdala in DSAP rats, despite significant loss of NST NA neurons and attenuated c-Fos activation of corticotropin-releasing hormone-positive neurons in the paraventricular nucleus of the hypothalamus (PVN). Thus, NST NA neurons contribute significantly to LiCl-induced hypophagia and recruitment of stress-responsive PVN neurons but appear to be unnecessary for CFA learning and expression. These findings support the view that distinct central nervous system circuits underlie LiCl-induced inhibition of food intake and conditioned avoidance behavior in rats.     

Involvement of noradrenergic transmission in the PVN on CREB activation, TORC1 levels, and pituitary-adrenal axis activity during morphine withdrawal

Experimental and clinical findings have shown that administration of adrenoceptor antagonists alleviated different aspects of drug withdrawal and dependence. The present study tested the hypothesis that changes in CREB activation and phosphorylated TORC1 levels in the hypothalamic paraventricular nucleus (PVN) after naloxone-precipitated morphine withdrawal as well as the HPA axis activity arises from α(1)- and/or β-adrenoceptor activation. The effects of morphine dependence and withdrawal on CREB phosphorylation (pCREB), phosphorylated TORC1 (pTORC1), and HPA axis response were measured by Western-blot, immunohistochemistry and radioimmunoassay in rats pretreated with prazosin (α(1)-adrenoceptor antagonist) or propranolol (β-adrenoceptor antagonist). In addition, the effects of morphine withdrawal on MHPG (the main NA metabolite at the central nervous system) and NA content and turnover were evaluated by HPLC. We found an increase in MHPG and NA turnover in morphine-withdrawn rats, which were accompanied by increased pCREB immunoreactivity and plasma corticosterone concentrations. Levels of the inactive form of TORC1 (pTORC1) were decreased during withdrawal. Prazosin but not propranolol blocked the rise in pCREB level and the decrease in pTORC1 immunoreactivity. In addition, the HPA axis response to morphine withdrawal was attenuated in prazosin-pretreated rats. Present results suggest that, during acute morphine withdrawal, NA may control the HPA axis activity through CREB activation at the PVN level. We concluded that the combined increase in CREB phosphorylation and decrease in pTORC1 levels might represent, in part, two of the mechanisms of CREB activation at the PVN during morphine withdrawal.     

Chronic intraparaventricular nuclear administration of orexin A in male rats does not alter thyroid axis or uncoupling protein-1 in brown adipose tissue

Orexin A, synthesised in the posterolateral hypothalamus, has widespread distribution including the paraventricular nucleus (PVN), which is rich in thyrotropin-releasing hormone (TRH) neurones. Nerve fibres in the PVN synapse on neurones that send polysynaptic projections to brown adipose tissue (BAT), which is important in thermogenesis. A number of observations suggests orexin A may be involved in regulation of metabolism and thermogenesis. We investigated the effect of orexin A injected intracerebroventricularly (ICV) on thyroid-stimulating hormone (TSH) and thyroid hormones in male rats. We then examined the effect of chronic iPVN injections of orexin A on plasma TSH and uncoupling protein-1 (UCP-1) protein in BAT. Orexin A (3 nmol) administered ICV significantly suppressed plasma TSH at 10 and 90 min. Orexin A (0.3 nmol) administered into the PVN twice daily for 3 days significantly increased day-time 2-h food intake, but did not significantly alter nocturnal food intake. Though chronic iPVN orexin A altered diurnal food intake, there was no effect on 24-h food intake or body weight. Furthermore, orexin A administered chronically into the PVN did not alter UCP-1 level in BAT, or plasma hormones relative to saline injected animals. Chronic iPVN orexin A does not appear to influence thermogenesis through activation of UCP-1 or the thyroid axis.     

Patterns of extracellular norepinephrine in the paraventricular hypothalamus: relationship to circadian rhythm and deprivation-induced eating behavior

In order to clarify the physiological role of norepinephrine (NE) in the hypothalamic paraventricular nucleus (PVN), changes in extracellular levels of endogenous NE were measured in 11 freely-moving rats using microdialysis and high pressure liquid chromatography with electrochemical detection. To determine whether there was a circadian pattern of extracellular NE in freely-eating subjects, samples of dialysate from the vicinity of the PVN were collected and assayed for NE every 2 hrs for 48 hrs. The pattern of NE averaged across subjects was similar during both 24-hr periods, with a reliable peak at the beginning of the dark cycle and relatively stable levels at all other times. When these animals were subsequently deprived of food for 24 hrs, a gradual rise in extracellular NE was observed, ultimately increasing to 215% of the predeprivation level. When the animals were refed and NE measurements were continued at more frequent intervals, extracellular levels were found to decline during the first 20 min of eating, as well as over the next 3 hrs as food intake diminished. These patterns of extracellular NE, together with previous evidence, suggest that endogenous NE in the PVN plays a role in the initiation and/or maintenance of normal eating behavior at the beginning of the nocturnal feeding period, as well as after food deprivation.