c-fos expression in the rat brain following central administration of neuropeptide Y and effects of food consumption

Administration of neuropeptide Y (NPY) intracerebroventricularly (i.c.v.) results in the release of a number of hypothalamic and pituitary hormones and stimulation of feeding and suppression of sexual behavior. In this study, we sought to identify cellular sites of NPY action by evaluating perikaryal Fos-like immunoreactivity (FLI), a marker of cellular activation, in those hypothalamic and extrahypothalamic sites previously implicated in the control of neuroendocrine function and feeding behavior. Additionally, we compared the topography of FLI in these brain sites when food was either available ad libitum or withheld after NPY injection (1 nmol/3 μl, i.c.v.). The results showed that one hour after NPY injection a large number of cells in the parvocellular region of the paraventricular nucleus (PVN) were FLI-positive in the absence of food consumption. However, in association with food intake, a significant number of cells were intensely stained in the magnocellular region of the PVN. An analogous increase in FLI in association with feeding was apparent in the supraotic nucleus (SON), the dorsomedial nucleus and the bed nucleus of the stria terminalis in the hypothalamus. Anong the extrahypothalamic sites, feeding facilitated FLI in a large number of cells located in the lateral subdivision of the central amygdaloid nucleus and the lateral subdivision of the solitary tract. FLI was observed in a moderate number of cells in the hypothalamic arcuate nucleus (ARC) and ventromedial nucleus, and this response was not changed by feeding. Cumulatively, these results show that neurons in a number of discrete hypothalamic and extrahypothalamic sites, previously implicated in the control of neuroendocrine function and feeding behavior, are activated by NPY and further, a divergent pattern of c-fos expression emerged in some of these sites if feeding occurs after NPY injection. Stimulation of FLI in cells of the PVN, SON and ARC by NPY imply the presence of NPY target cells that play a role in the neuroendocrine control of pituitary function. The finding that NPY induced FLI in cells located in the parvocellular subdivision of the PVN even in the absence of feeding, imply that cells involved in initiation of food intake by NPY may reside in this subdivision of the PVN. On the other hand, the appearance of Fos-cells in the magnocellular subdivision of the PVN in response to feeding, suggests neural mechanisms that operate during the post-ingestion period, including those associated with termination of NPY-induced feeding, may impinge upon this subdivision of the PVN.     

Nicotine administration decreases neuropeptide Y expression and increases leptin receptor expression in the hypothalamus of food-deprived rats

The effects of nicotine on the expressions of neuropeptide Y (NPY) and leptin receptor in the rat hypothalamus were investigated via immunohistochemistry. The results show that NPY expression is not affected in the arcuate nucleus (ARN) and is increased only slightly in the paraventricular nucleus (PVN) by nicotine administration under normal (i.e. fed) conditions and that leptin receptor expression is decreased slightly in the ARN and not affected in the PVN following nicotine treatment under the same conditions. Food deprivation enhanced NPY and suppressed leptin receptor expression in the ARN and PVN of the hypothalamus. Nicotine administration resulted in decreased NPY and increased leptin receptor levels.     

Involvement of hypothalamic neuropeptide Y in pentazocine induced suppression of food intake in rats

The potent orexigenic peptide neuropeptide Y (NPY) has been considered as a possible endogenous ligand for a subpopulation of sigma receptors (SigR). However, their mutual interaction with reference to feeding behavior remains poorly understood. In the present study, we explored the possible interaction between sigma1 receptors (Sig1R) agonist, pentazocine, and NPY on food intake in satiated rats. While pentazocine dose-dependently reduced the food intake, NPY significantly increased it at 2, 4 and 6 h post injection time points. In combination studies, pretreatment with NPY (0.1 nmol/rat, intra-PVN) normalized the inhibitory effect of pentazocine (60 μg/rat, intra-PVN) on food intake. Similarly, pre-treatment with pentazocine (30 μg/rat, intra-PVN) significantly antagonized the orexigenic effect of NPY (0.5 and 1.0 nmol/rat, intra-PVN). Moreover, pentazocine treatment decreased NPY immunoreactivity in arcuate (ARC), paraventricular (PVN), dorsomedial (DMH) and ventromedial (VMH) nuclei of hypothalamus. However, no change was observed in lateral hypothalamus (LH). Study implicates the reduced NPY immunoreactivity for the anorectic effect observed following pentazocine injections. Therefore, the concomitant activation of the NPYergic system along with the Sig1R agonist treatment may serve a useful purpose in the management of the unwanted side effects related to energy homeostasis.     

Increased feeding and neuropeptide Y (NPY) but not NPY mRNA levels in the hypothalamus of the rat following central administration of the serotonin synthesis inhibitorp-chlorophenylalanine

Neurons containing serotonin (5-HT), a potent anorexic agent, come into contact with neuropeptide Y-ergic neurons, that project from the arcuate nucleus (ARC) to the paraventricular nucleus (PVN). NPY powerfully stimulates feeding and induces obesity when injected repeatedly into the PVN. We hypothesize that 5-HT tonically inhibits the ARC-PVN neurons and that balance between the two systems determines feeding and energy homeostasis. This study aimed to determine whether central injection of the 5-HT synthesis inhibitor p-chlorophenylalanine (pCPA), which increases feeding, increased hypothalamic NPY and NPY mRNA levels. pCPA (10 mg/kg in 3 μl) was administered into the third ventricle either as a single injection (n = 8) or daily for 7 days (n = 8). Control rats received a similar injection of saline. pCPA significantly increased food intake compared with controls after both single and repeated injections (P < 0.05). NPY levels were measured by radioimmunoassay in microdissected hypothalamic extracts. NPY levels in the acutely treated group were significantly increased in the paraventricular nucleus (PVN; by 41%,P = 0.01), anterior hypothalamic area (AHA; by 34%,P < 0.01) and lateral hypothalamic area (LHA; by 41%,P < 0.02). In the 7-day-treated group, NPY levels were also increased in the same areas, i.e. PVN (by 24%,P < 0.01), AHA (by 30%,P < 0.01) and LHA (by 38%,P = 0.01). There were no significant changes in the ARC or any other region or in hypothalamic NPY mRNA levels. pCPA administration increased NPY levels in several regions notably the PVN. This is a major site of NPY release, where NPY injection induces feeding. We suggest that the hyperphagia induced by pCPA is mediated by increased NPY levels and secretion in the PVN. This is further evidence for interactions between NPY and 5-HT in the control of energy homeostasis.     

Immunohistochemical analysis of the ontogeny of neuropeptide Y immunoreactive neurons in foetal rat brain

The development of neuropeptide Y-like immunoreactive structures in the foetal rat brain was investigated by means of the indirect immunohistofluorescence technique.Neuropeptide Y-like immunoreactive cells and fibres first appeared on day 13 of gestation, in the solitary tract nucleus, lateral reticular nucleus and nucleus ambiguus in the medulla oblongata, and in the primordial inferior colliculus and deep mesencephalic nucleus. Thereafter, neuropeptide Y-like immunoreactive cells and fibres increased in number in many areas including the primary olfactory cortex, the frontoparietal, somatosensory cortex, caudate putamen, lateral hypothalamus, ventrolateral thalamus, amygdala and parafascicular nucleus. The maximum number of cells over the age range studied, namely day 12 of gestation to birth day, occurred at around day 21. On the day of birth, accordingly, there were significantly fewer neuropeptide Y-like immunoreactive cell bodies in a number of brain areas, the most striking deficit being in the ventrolateral thalamus.The present study demonstrates the very early appearance of neuropeptide Y-like immunoreactive structures during foetal brain development. The functional role of the peptide during this period remains, however, to be determined.     

Developmental increases in hypothalamic neuropeptide Y content with the embryonic age of meat- and layer-type chicks

We determined central neuropeptide Y (NPY) content of meat- and layer-type chicks at embryonic days 7, 14, 20, and at post-hatching day 1. The central NPY was detectable at day 7; hypothalamic NPY content developmentally increased with a similar pattern but a different level between both types of chicks. These results were discussed with respect to feeding behavior early period after hatching.     

Elevated neuropeptide Y and corticotropin-releasing factor in the brain of a novel epileptic mutant rat: Noda epileptic rat

Noda epileptic rat (NER) is a new epileptic rat strain, which was developed by inbreeding rats with spontaneous tonic-clonic seizures in a stock of Crj:Wistar. In the present study, possible changes of two neuropeptides, neuropeptide Y (NPY) and corticotropin-releasing factor (CRF), in the brains of NER were investigated. Increased contents of immunoreactive (IR) NPY were found in the striatum and amygdala of 8-week NERs with partial seizure, while these changes extended to the limbic region including hippocampus in 16-week NERs with fully developed generalized tonic-clonic seizure. IR-CRF were elevated only in the entorhinal and pyriform cortex of both 8-week and 16-week NERs. Generalized tonic-clonic seizure in NERs induced a transient increase of NPY mRNA in the granular layer of dentate gyrus. These results suggest that NPY metabolism in the limbic brain contributes to the seizure susceptibility in this model of epilepsy.     

The distribution of neuropeptide Y and brain-derived neurotrophic factor immunoreactivity in hippocampal formation of the monkey and rat

The distribution of neuropeptide Y (NPY) and Brain-Derived Neurotrophic Factor (BDNF) in the hippocampal formation of monkey and rat brains was studied immunohistochemically. The NPY-neuronal system is more highly developed in the monkey compared to that in the rat. The distribution of NPY-positive products was coincident with that of abundant BDNF-positive deposits. These observations suggest that the role of BDNF and the interaction of BDNF-NPY may differ between species.     

Distribution and characterization of neuropeptide Y-like immunoreactivity in the brain of the crested newt

The newt brain represents a simplified model for the increasingly complex vertebrate neuronal organization. The localization of neuropeptide Y-like (NPY-like) containing neurons in the brain of Triturus cristatus was studied by means of indirect immunofluorescence, peroxidase-antiperoxidase, and avidin-biotin techniques using a highly specific antiserum. NPY-like positive cell bodies were observed in several areas, most notably in the telencephalon (primordium hippocampi and amygdaloid complex), the preoptic and suprachiasmatic areas, the hypothalamus, the dorsal thalamus, the tegmentum, and the rhombencephalon (laterolateral grey column and raphe area). Nerve fibres were particularly abundant in the pallium, striatum, septum, amygdaloid, preoptic neuropils, and pars intercalaris diencephali. Bundles of NPY-immunoreactive fibres also were visualized in the dorsal thalamus and in the posterior hypothalamus. The pars intermedia lacked any NPY-like positive fibres. Neuronal processes also were found in the tectum mesencephali and in the body of the cerebellum. A prominent NPY-like fibre network was observed in the octavolateralis. Concentrations of NPY measured by means of a specific radioimmunoassay were threefold higher in the hypothalamus (15.2 +/- 1.3 ng/mg proteins) than in the rhombencephalon (4.9 +/- 0.3) and the mesencephalon (4.3 +/- 0.2). The concentration found in the telencephalon was 2.1 +/- 0.3 ng/mg proteins. Sephadex G-50 gel chromatography of whole brain extracts indicated the presence of high molecular weight forms of NPY-like material in addition to the authentic peptide. Both amphibian and mammalian NPY peptides had an apparent molecular weight of 4,000 daltons, as evidenced by immunoblotting analysis. High-performance liquid chromatography demonstrated, however, that the newt peptide was slightly less hydrophobic than porcine NPY. The present findings indicate that NPY-immunoreactive neurons are widely distributed in the brain of urodeles. Our data indicate that the NPY molecule has been relatively well preserved during evolution.     

Hypothalamic neuropeptide Y, its gene expression and receptor activity: relation to circulating corticosterone in adrenalectomized rats

Previous evidence has suggested a possible relationship between the adrenal steroid, corticosterone (CORT) and neuropeptide Y (NPY) in the brain. To provide a more systematic analysis of this interaction, the present study employed a variety of techniques, including in sity hybridization to measure NPY gene expression, radioimmunoassay to examine peptide levels and radioligand [¹²⁵I]peptide YY (PYY) binding for analysis of peptide receptors. The results show that adrenalectomy (ADX), which caused a decline in CORT to levels < 0.3 μg%, has generally little impact on the hypothalamic NPY projection system under normal, basal conditions. This includes peptide gene expression or content in the area of its cell bodies (arcuate nucleus, ARC), in addition to peptide binding at its receptor sites. While it also includes peptide content at most hypothalamic terminal sites, there are three notable exceptions, namely, the medial paraventricular (PVN) and dorsomedial nuclei and medial preoptic area, where NPY nerve terminals and glucocorticoid receptors are particularly dense and the decline in CORT through ADX markedly reduces NPY content. In contrast, evidence obtained from CORT replacement in ADX rats shows that this steroid has profound impact on all components of the hypothalamic NPY system. This peptide-steroid interaction is apparent at the level of the cell body (ARC), as well as at the nerve terminal or receptor site (PVN and ARC), where CORT levels > 10 μg% strongly potentiate NPY gene expression, peptide content and radioligand binding. These and other findings suggest that this CORT-NPY interaction in the hypothalamus occurs physiologically under conditions, e.g., at the onset of the active feeding cycle, when circulating CORT normally rises.     

Increased neuropeptide Y secretion in the hypothalamic paraventricular nucleus of obese (fa/fa) Zucker rats

NPY is synthesized in the hypothalamic arcuate nucleus (ARC), and NPY injected into the paraventricular nucleus (PVN), the main site of NPY release, induces hyperphagia and reduces energy expenditure. Hypothalamic NPY and mRNA and NPY levels are increased in fatty Zucker rats, consistent with increased NPY release. This could explain the hyperphagia and reduced energy expenditure, which lead to obesity in the fatty Zucker rat. We have therefore compared NPY secretion in the PVN of conscious fatty and lean Zucker rats using push-pull sampling. The NPY secretory profile was consistently higher in fatty Zucker rats than in lean rats throughout the 3-h study period (P < 0.01), and mean NPY secretion over the whole 3 h was increased 2-fold in the fatty rats (P < 0.001). We conclude that fatty Zucker rats have increased NPY release in the PVN. This observation further supports the hypothesis that increased activity of the NPYergic ARC-PVN pathway may contribute to obesity in the fatty Zucker syndrome.     

Resistance to diet-induced obesity is associated with increased proopiomelanocortin mRNA and decreased neuropeptide Y mRNA in the hypothalamus

Mechanisms mediating genetic susceptibility to diet-induced obesity have not been completely elucidated. Elevated hypothalamic neuropeptide Y (NPY) and decreased hypothalamic proopiomelanocortin (POMC) are thought to promote the development and maintenance of obesity. To assess the potential role of hypothalamic neuropeptide gene expression in diet-induced obesity, the present study examined effects of a high-fat diet on hypothalamic NPY and POMC mRNA in three strains of mice that differ in susceptibility to develop diet-induced obesity. C57BL/6J, CBA, and A/J mice were fed either normal rodent chow or a high-fat diet for 14 weeks after which hypothalamic gene expression was measured. On the high-fat diet, C57BL/6J mice gained the most weight, whereas A/J mice gained the least weight. On the high-fat diet, NPY mRNA significantly decreased as body weight increased in CBA and A/J mice, but not in C57BL/6J mice. In addition, POMC mRNA significantly increased as body weight increased in A/J mice, but not in CBA and C57BL/6J mice. Since decreased NPY mRNA and increased POMC mRNA would presumably attenuate weight gain, these results suggest that a high-fat diet produces compensatory changes in hypothalamic gene expression in mice resistant to diet-induced obesity but not in mice susceptible to diet-induced obesity.     

Distribution of neuropeptide Y-like immunoreactivity in the normoganglionic and aganglionic segments of human colon

Summary The localisation and distribution of neuropeptide Y (NPY)-like immunoreactivity were studied by use of immunohistochemical methods in gut tissues from 19 patients with Hirschsprung's disease, including 4 cases of long segment aganglionosis. In the normoganglionic segment, immunoreactive cell bodies and nonvaricose processes were seen within both myenteric and submucous plexuses. A scarce supply of varicose fibres was found in the lamina propria mucosae, muscularis mucosae and longitudinal muscle layer. NPY fibres were more frequently encountered in the circular muscle layer, although with a weakly immunostaining intensity. In addition, blood vessels in the submucosal connective tissue were surrounded by a typical plexus of varicose, NPY-positive fibres. Immunoreactive endocrine cells could be detected in the colonic epithelium. In the aganglionic segment, numerous nerve fasciculi comprising a small to moderate number of NPY fibres with varicosities were observed throughout the entire layer of the colonic wall. A few varicose, NPY-positive fibres were also contained in the relatively large, hypertrophic nerve fasciculi located in the intermuscular zone and submucosal connective tissue. NPY-immunoreactive fasciculi were more densely distributed in the distal aganglionic segment than in the proximal aganglionic one. On the other hand, the distribution of NPY-positive fibres in long segment aganglionosis was quite different from that in short segment type; in cases of long segment type, no immunoreactive nerve fibres were detected within the circular muscle layer of the proximal aganglionic segment near the oligoganglionic segment and only a few fibres were observed within the hypertrophic nerve bundle of the intermuscular zone. The present results suggest that NPY-like immunoreactive nerves in the human colon have a dual origin of intrinsic and extrinsic elements. The origin and nature of extrinsic NPY nerve fibres in the human colon are discussed.     

Weight loss in rats treated with intracerebroventricular cobalt protoporphyrin is not specific to the neuropeptide Y system

Cobalt protoporphyrin (CoPP) reduces food intake and body weight following intracerebroventricular (i.c.v.) administration in rats. We injected 0.2 μmol CoPP per kg body weight i.c.v. and monitored body weight and daily food intake for 7 days. The body weight and 24 h food intake of CoPP-treated animals was significantly lower than that of vehicle-treated animals in all studies (P < 0.01) from day 2 to day 7. The 2 h feeding response (CoPP vs. vehicle-treated) to 10 μg neuropeptide Y (NPY) (4.0 vs. 7.1 g;P < 0.05), the 1 h feeding response to 10 μg galanin (1.3 vs. 3.2 g;P < 0.05) and 30 μg norepinephrine (0.6 vs. 1.9 g;P < 0.05) in CoPP-treated animals were all reduced compared to the vehicle-treated group. In addition there was no change in hypothalamic NPY mRNA in CoPP-treated animals. I.c.v. COP decreases sensitivity to exogenous NPY, galanin and norepinephrine. The effect of COP is not specific to NPY as previously described.     

Upregulation of brain somatostatin and neuropeptide Y following lidocaine-induced kindling in the rat

Male Sprague-Dawley rats received a daily injection of 60 mg/kg of lidocaine (> 30 days). Twenty percent of rats developed convulsions (kindled rats) and remaining rats did not show convulsions (non-kindled rats). The level of immunoreactive somatostatin (IR-SRIF) in kindled rats was significantly increased in amygdala than that in non-kindled rats and control rats. Immunoreactive neuropeptide Y (IR-NPY) contents in kindled rats were significantly increased in amygdala, hippocampus, cortex and striatum compared to non-kindled and control rats. The expression of SRIF mRNA in kindled rats produced a significant increase in amygdala, while NPY mRNA in kindled rats showed an elevated expression in both amygdala and hippocampus. These results coincide with the previous findings with the elevated expression of SRIF and NPY mRNA in electrically and pharmacologically kindled models, suggesting the important role of these peptides in the kindling phenomenon.     

癫痫动物模型脑中神经肽Y的动态含量变化及意义

目的:探讨匹罗卡品(PILO)诱发的癫痫大鼠模型脑组织中神经肽Y(Neuropeptide Y,NPY)含量的动态变化及意义,进一步明确NPY与癫痫的关系,为抗癫痫治疗,研制抗癫痫药物提供新途径。方法:健康成年雄性SD大鼠120只,随机分为两组:单纯腹腔注射匹罗卡品组(癫痫模型组);单纯腹腔注射生理盐水组(对照组);注射后根据Racine制定的标准判定是否有癫痫发作,并行脑电图检查,观察有无癫痫样波(棘波,尖波,棘慢波,尖慢波)发放。两组大鼠分别于给药后1h,3h,6h,24h,3d,7d,15d,30d,60d将大鼠麻醉,取出脑组织,对脑组织中的NPY含量进行测定。结果:癫痫模型组60只大鼠中,2只死于癫痫持续状态,其余大鼠可观察到边缘发作行为表现,脑电图有典型的癫痫样波发放,对照组无癫痫发作及癫痫样波发放。癫痫模型组脑NPY含量与对照组相比,差异有显著性P<0.05;癫痫模型组急性期(1h-7d)与慢性期(15d-60d)比较差异有显著性P<0.05,对照组差异无显著性;癫痫模型组与对照组脑中的NPY含量在12h,24h,15d,30d,60d.差异有显著性P<0.05或P<0.01,癫痫模型组脑中的NPY含量各组(各时间段)比较有差异有显著性P<0.05,对照组差异无显著性,癫痫模型组大鼠Ⅳ-Ⅴ级发作与Ⅱ-Ⅲ级发作,脑NPY含量比较,差异有显著性P<0.05。结论:1.神经肽Y与癫痫密切相关,癫痫发作后?     

Central insulin inhibits hypothalamic galanin and neuropeptide Y gene expression and peptide release in intact rats

The central actions of insulin, on galanin (GAL) and neuropeptide Y (NPY) in the brain, are examined in intact satiated rats. Ventricular injections of insulin reduce both GAL and NPY gene expression and immunoreactivity in different hypothalamic areas but have no effect in extra-hypothalamic sites. Insulin applied to medial hypothalamic fragments in vitro significantly reduces GAL and NPY release. This evidence suggests that insulin acts centrally and directly on hypothalamic peptide activity under normal feeding conditions.     

A putative morphological substrate of the catecholamine-influenced neuropeptide Y (NPY) release in the human hypothalamus

Neuropeptide Y (NPY) is a 36 amino acid peptide, which among others, plays a pivotal role in stress response. Although previous studies confirmed that NPY release is increased by stress in several species, the exact mechanism of the stress-induced NPY release has not been elucidated yet.In the present study, we examined, with morphological means, the possibility that catecholamines directly influence NPY release in the human hypothalamus. Since the use of electron microscopic techniques is virtually impossible in immunostained human samples due to the long post mortem time, double-label immunohistochemistry was utilised in order to reveal the putative catecholaminergic-NPY associations.The present study is the first to demonstrate juxtapositions between the catecholaminergic, tyrosine hydroxylase (TH)/dopamine-beta hydroxylase (DBH)-immunoreactive (IR) and NPY-IR neural elements in the human hypothalamus. These en passant type associations are most numerous in the infundibular and periventricular areas of the human diencephalon. Here, NPY-IR neurons often form several contacts with catecholaminergic fibre varicosities, without any observable gaps between the contacting elements, suggesting that these juxtapositions may represent functional synapses. The lack of phenylethanolamine N-methyltransferase (PNMT)-NPY juxtapositions and the relatively few observed DBH-NPY associations suggest that the vast majority of the observed TH-NPY juxtapositions represent dopaminergic synapses. Since catecholamines are known to be the crucial components of the stress response, the presence of direct, catecholaminergic (primarily dopaminergic)-NPY-IR synapses may explain the increased NPY release during stress. The released NPY in turn is believed to play an active role in the responses that are directed to maintain the homeostasis during stressful conditions.     

Distribution of NPY Y5-like immunoreactivity in the rat brain

The pharmacology and brain mRNA distribution of the neuropeptide Y (NPY) rat Y5 (rY5) receptor has led to the hypothesis that this receptor might mediate the hypothalamic feeding response to NPY in addition to many other physiologic functions. However, through the use of autoradiographic techniques, only very low levels of Y5-like immunoreactive (Y5-ir) binding are detected in the rat brain. To localize the Y5 protein in the rat brain, polyclonal antibodies were raised to the carboxyl terminus of the rY5 receptor. The resulting antisera were affinity purified and characterized by specific binding to HEK293 cells that had been stably transfected with the rY5 receptor. Utilizing immunohistochemical techniques, we found a discrete pattern of Y5-ir in the rat brain. In initial studies, very low levels of Y5-ir were detected, and TSA amplification was required to visualize the staining. Areas with the highest levels of expression in clude the piriform cortex, supraoptic nucleus, and hippocampus. Areas with moderate levels of expression include the lateral septum, amygdala, arcuate nucleus, paraventricular hypothalamic nucleus, locus coeruleus, and cerebellum. With several exceptions, this pattern of distribution is consistent with earlier reports of rY5 mRNA and receptor protein expression.     

Circadian control during the day and night: Role of neuropeptide Y Y5 receptors in the suprachiasmatic nucleus

Circadian rhythms are reset by light during the night or by nonphotic stimuli during the day. Neuropeptide Y (NPY), which appears to mediate at least some nonphotic phase shifts by its actions in the suprachiasmatic nucleus (SCN), induces phase advances during the day and inhibits light-induced phase advances during the night. In this study, we used a highly selective Y5-like agonist to test whether activation of NPY Y5 receptors is sufficient to mimic NPY during the day and late night in Syrian hamsters. We also tested whether NPY in the early night reduces light-induced phase delays in a dose-dependent manner. Microinjection of a selective Y5 receptor agonist, (Ala(31), Aib(32))-NPY, into the SCN significantly inhibited light-induced phase advances during the late night, but did not induce phase advances during the day. In addition, concentrations of NPY ranging from 0.23 to 23 mM did not attenuate light-induced phase delays in the early night. These results suggest that activation of Y5-like receptors is sufficient to inhibit light-induced phase advances during the late night but is not sufficient to induce phase advances during the day. Furthermore, this study provided no evidence that NPY can inhibit light-induced phase shifts early in the night.