Intracerebroventricular Administration Of Neuropeptide Y Research Articles

Neuropeptide Y as Alternative Pharmacotherapy for Antidepressant-Resistant Social Fear.

In many social anxiety disorder (SAD) patients, the efficacy of antidepressant therapy is unsatisfactory. Here, we investigated whether mice deficient for the lysosomal glycoprotein acid sphingomyelinase (ASM−/−) represent an appropriate tool to study antidepressant-resistant social fear. We also investigated whether neuropeptide Y (NPY) reduces this antidepressant-resistant social fear in ASM−/− mice, given that NPY reduced social fear in a mouse model of SAD, namely social fear conditioning (SFC). We show that neither chronic paroxetine nor chronic amitriptyline administration via drinking water were successful in reducing SFC-induced social fear in ASM−/− mice, while the same treatment reduced social fear in ASM+/− mice and completely reversed social fear in ASM+/+ mice. This indicates that the antidepressants paroxetine and amitriptyline reduce social fear via the ASM-ceramide system and that ASM−/− mice represent an appropriate tool to study antidepressant-resistant social fear. The intracerebroventricular administration of NPY, on the other hand, reduced social fear in ASM−/− mice, suggesting that NPY might represent an alternative pharmacotherapy for antidepressant-resistant social fear. These results suggest that medication strategies aimed at increasing brain NPY concentrations might improve symptoms of social fear in SAD patients who fail to respond to antidepressant treatments.

Interaction of Cocaine- and Amphetamine-regulated Transcript and Neuropeptide Y on Behavior in the Central Nervous System.

In the central nervous system, cocaine- and amphetamine-regulated transcript (CART) 55-102 peptide is localized in areas, such as the ventral tegmental area, amygdala, hypothalamus, and hippocampus, where emotional activity is regulated. Studies on the effects of the intracerebroventricular (ICV) administration of CART peptide on behavior remain limited. The findings from these studies suggest that this neuropeptide has anxiogenic-like effects. In the central nervous system, neuropeptide Y (NPY) has similar localization as CART. Previous behavioral studies have demonstrated that the ICV administration of NPY has anxiolytic-like effects. In our study, we established five experimental groups of male Wistar rats to study the competitive effects of NPY and CART peptide. These groups were sham (n=10), CART (n=10), NPY (n=10), CART-NPY (n=10), and NPY-CART (n=10). The open field test, elevated plus maze test, and Porsolt swim test were performed for behavioral analyses. Moreover, the rats were decapitated after the behavioral tests, and the amount of these two peptide in their brains was quantified. Our study revealed that the ICV administration of CART peptide is anxiogenic and inhibits animals undergoing learned helplessness in the Porsolt swim test. When we evaluated the results of our study with respect to NPY, we observed its anxiolytic-like effects; in the Porsolt swim test, although it reduced the duration of immobilization, it did not affect the period of struggle. Our results revealed that during the competitive interaction of these two peptides, anxiogenic CART peptide suppressed the anxiolytic effects of NPY.

Adenoviral-mediated placental gene transfer of igf-1 corrects placental insufficiency via restoring placental endothelial progenitor cells

Neuropeptide Y (NPY) has been established as an important regulator of food intake in mammals. However, the involvement of NPY in the feeding behavior of fish has not yet been fully understood. The present study investigated the role of NPY in food intake in grass carp. The full-length cDNA sequence of gc-NPY was 797 bp, and an ORF of 96 amino acids, including the 28-residue signal peptide and 36-residue mature peptide, which had high identities to the NPY of cyprinid fishes. Two receptors Y1 and Y5 which mediate the appetite-stimulating effects of NPY in mammals lost from some of the euteleost genomes. However, sequences of other NPY receptors Y8a and Y8b were obtained from the ESTs library of grass carp in our previous studies. NPY and both Y8 receptors were predominantly expressed in the brain. Cumulative food intake was significantly increased by intracerebroventricular administration of NPY during a 72-h observation period. For better understanding of NPY's action in grass carp, the mRNA levels of appetite regulators, energy metabolism genes and key digestive enzymes were assessed. The results showed that the mRNA levels of Y8b were significantly increased, while the expressions of cholecystokinin (CCK), cocaine and amphetamine regulated transcript (CART), pituitary adenylate cyclase-activating peptide (PACAP), leptin, leptin receptor (leptinR) and leptin receptor overlapping transcript protein (LEPROT) were significantly decreased after NPY injection. In addition, the marked stimulation of insulin-like growth factor1 (IGF1), insulin-like growth factor 1 receptor (IGF1R), lipoprotein lipase (LPL), Stearoyl-CoA desaturase 1 (SCD1), amylase and trypsin mRNA levels in liver were caused by NPY administration, and the mRNA level of uncoupling protein 1(UCP 1) tended to decrease but not significantly. These results indicate that NPY acts as an orexigenic factor in the grass carp, and Y8b may involve in the feeding regulation. NPY not only affects food intake, but also has marked effects on energy metabolism in grass carp. Moreover, NPY seems to closely interact with other appetite regulators, and the present results provide novel insight into these complex interactions. Further understandings of appetite regulation in fish ultimately have the potential to yield methods for improving feed efficiency in aquaculture.

Effect of neuropeptide Y on food intake in bullfrog larvae

Neuropeptide Y (NPY) is a potent orexigenic neuropeptide implicated in appetite regulation in mammals. However, except for teleost fish such as the goldfish and zebrafish, the involvement of NPY in the regulation of feeding in non-mammalian vertebrates has not been well studied. Anuran amphibian larvae feed and grow during the pre- and pro-metamorphic stages, but, thereafter they stop feeding as the metamorphic climax approaches. Therefore, orexigenic factors seem to play important roles in pre- and pro-metamorphic larvae. We investigated the role of NPY in food intake using bullfrog larvae including pre- and pro-metamorphic stages, and examined the effect of feeding status on the expression level of the NPY transcript in the hypothalamus. NPY mRNA levels in hypothalamus specimens obtained from larvae that had been fasted for 3 days were higher than those in larvae that had been fed normally. We then investigated the effect of intracerebroventricular (ICV) administration of NPY on food intake in the larvae. Cumulative food intake was significantly increased by ICV administration of NPY (5 and 10pmol/g body weight, BW) during a 15-min observation period. The NPY-induced orexigenic action (10pmol/g BW) was blocked by treatment with a NPY Y1 receptor antagonist, BIBP-3226 (100pmol/g BW). These results indicate that NPY acts as an orexigenic factor in bullfrog larvae.

Neuropeptide Y stimulates food intake and regulates metabolism in grass carp, Ctenopharyngodon idellus

Neuropeptide Y (NPY) has been established as an important regulator of food intake in mammals. However, the involvement of NPY in the feeding behavior of fish has not yet been fully understood. The present study investigated the role of NPY in food intake in grass carp. The full-length cDNA sequence of gc-NPY was 797bp, and an ORF of 96 amino acids, including the 28-residue signal peptide and 36-residue mature peptide, which had high identities to the NPY of cyprinid fishes. Two receptors Y1 and Y5 which mediate the appetite-stimulating effects of NPY in mammals lost from some of the euteleost genomes. However, sequences of other NPY receptors Y8a and Y8b were obtained from the ESTs library of grass carp in our previous studies. NPY and both Y8 receptors were predominantly expressed in the brain. Cumulative food intake was significantly increased by intracerebroventricular administration of NPY during a 72-h observation period. For better understanding of NPY's action in grass carp, the mRNA levels of appetite regulators, energy metabolism genes and key digestive enzymes were assessed. The results showed that the mRNA levels of Y8b were significantly increased, while the expressions of cholecystokinin (CCK), cocaine and amphetamine regulated transcript (CART), pituitary adenylate cyclase-activating peptide (PACAP), leptin, leptin receptor (leptinR) and leptin receptor overlapping transcript protein (LEPROT) were significantly decreased after NPY injection. In addition, the marked stimulation of insulin-like growth factor1 (IGF1), insulin-like growth factor 1 receptor (IGF1R), lipoprotein lipase (LPL), Stearoyl-CoA desaturase 1 (SCD1), amylase and trypsin mRNA levels in liver were caused by NPY administration, and the mRNA level of uncoupling protein 1(UCP 1) tended to decrease but not significantly. These results indicate that NPY acts as an orexigenic factor in the grass carp, and Y8b may involve in the feeding regulation. NPY not only affects food intake, but also has marked effects on energy metabolism in grass carp. Moreover, NPY seems to closely interact with other appetite regulators, and the present results provide novel insight into these complex interactions. Further understandings of appetite regulation in fish ultimately have the potential to yield methods for improving feed efficiency in aquaculture.

Hypothalamic Y2 receptors regulate bone formation.

Neuropeptide Y (NPY) is a downstream modulator of leptin action, possibly at the level of the arcuate nucleus where NPY neurons are known to express both leptin receptors and Y2 receptors. In addition to the well-described role of NPY and leptin in energy balance and obesity, intracerebroventricular administration of NPY or leptin also causes bone loss. Here we show that Y2 receptor-deficient mice have a twofold increase in trabecular bone volume as well as greater trabecular number and thickness compared with control mice. We also demonstrate that central Y2 receptors are crucial for this process, since selective deletion of hypothalamic Y2 receptors in mature conditional Y2 knockout mice results in an identical increase in trabecular bone volume within 5 weeks. This hypothalamus-specific Y2 receptor deletion stimulates osteoblast activity and increases the rate of bone mineralization and formation, with no effect on osteoblast or osteoclast surface measurements. The lack of any changes in plasma total calcium, leptinemia, or hypothalamo-pituitary-corticotropic, -thyrotropic, -somatotropic, or -gonadotropic output suggests that Y2 receptors do not modulate bone formation by humoral mechanisms, and that alteration of autonomic function through hypothalamic Y2 receptors may play a key role in a major central regulatory circuit of bone formation.

Neuropeptide Y-Y1 receptor modulates nitric oxide level during stroke in the rat

In a rat endovascular middle cerebral artery occlusion (MCAO) stroke model, we previously showed that intracerebroventricular (ICV) injection of neuropeptide Y (NPY) or an Y1 receptor agonist, [Leu 31,Pro 34]-NPY, increased the infarct volume, that an Y1 receptor antagonist, BIBP3226, reduced the infarct volume, and that an Y2 receptor agonist, NPY3-36, had no effect. In this study, we used electron paramagnetic resonance (EPR) spectroscopy to measure nitric oxide (NO) and examined how ICV administration of NPY or its receptor analogs would modulate the brain NO level between the bregma levels +2 and −4 mm during MCAO, since excessive NO mediates ischemic damage. The relative brain NO concentration was increased to 131.94 ± 7.99% (mean ± SEM; n = 8) at 15 min of MCAO. NPY treatment further increased the relative brain NO concentration to 250.94 ± 50.48% ( n = 8), whereas BIBP3226 significantly reduced the brain NO concentration to 69.63 ± 8.84% ( n = 8). [Leu 31,Pro 34]-NPY (137.61 ± 14.54%; n = 7) or NPY3-36 (129.23 ± 21.77%; n = 8) did not affect the brain NO concentration at 15 min of MCAO. Our results suggest that the NPY-Y1 receptor activation mediates ischemic injury via NO overproduction and that inhibition of the Y1 receptor may confer protection via suppression of excessive NO production during ischemia.

Increases in Sucrose Consumption, But Not Ethanol Consumption, Following ICV NPY Administration

Neuropeptide Y (NPY) is a centrally acting neuromodulator that influences both consummatory behaviors and anxiety. NPY's effects on feeding are primarily regulated through Y5 receptors in hypothalamic sites, whereas NPY-induced anxiolysis appears to be mediated by Y1 receptors in the amygdala. Recently, NPY has been postulated to play a role in the regulation of ethanol consumption. The present study assessed the influence of intracerebroventricular (ICV) administration of NPY on the consumption of 10% ethanol or 2% sucrose in rats. Male Wistar rats were trained to self-administer 10% ethanol using the sucrose-substitution procedure and then implanted with an intracerebroventricular (ICV) cannula. The effects of NPY (0–15 μg) on ethanol consumption and sucrose consumption were then examined. ICV NPY infusion had no significant effects on the consumption of 10% ethanol, however, NPY significantly increased the consumption of 2% sucrose, [ F(1, 11) = 6.18, p = 0.03]. These data suggest that ethanol intake and sucrose intake are differentially regulated by NPY. It is hypothesized that ICV infusion of NPY may be affecting both Y1 and Y5 receptors producing increased consummatory drive and anxiolysis, two factors that have opposing effects on subsequent ethanol consumption. Therefore, additional studies including site specific injection of NPY will be necessary to provide further insight into the role of NPY on ethanol consumption.

L-152,804: Orally Active and Selective Neuropeptide Y Y5 Receptor Antagonist

Neuropeptide Y (NPY) elicits food intake through the action of hypothalamic G-protein-coupled receptors. Previous publications indicate that the Y5 receptor may represent one of these postulated hypothalamic “feeding” receptors. Using a potent and orally available Y5 antagonist L-152,804, we evaluated the involvement of the Y5 receptor in feeding regulation. L-152,804 displaced [125I]peptide YY (PYY) binding to human and rat Y5 receptors with Ki values of 26 and 31 nM, respectively, and inhibited NPY (100 nM)-induced increase in intracellular calcium levels via human Y5 receptors (IC50 = 210 nM). L-152,804 did not show significant affinity for human Y1, Y2, and Y4 receptors at a dose of 10 μM. Intracerebroventricular (ICV) (30 μg) or oral (10 mg/kg) administration of L-152,804 significantly inhibited food intake evoked by ICV-injected bovine pancreatic peptide (bPP, 5 μg; a moderately selective Y4, Y5 agonist) in satiated SD rats. However L-152,804 did not significantly inhibit ICV NPY (5 μg; a Y1, Y2, Y5 agonist)-induced food intake. These findings suggest that L-152,804 is a selective and potent non-peptide Y5 antagonist with oral bioavailability and brain penetrability. In addition, the anorexigenic effects of L-152,804 on bPP-induced feeding revealed participation of the Y5 receptor in feeding regulation, while ICV administration of NPY does not appear to significantly contribute to Y5 stimulated food intake. We conclude that the potent and orally active Y5 antagonist, L-152,804, represents a useful tool to address the physiological role of the Y5 receptor.

Inhibition by neuropeptide Y of fentanyl-induced muscular rigidity at the locus coeruleus in rats

The aim of this study was to evaluate the effects of centrally administered neuropeptide Y (NPY) on muscular rigidity induced by fentanyl in Sprague–Dawley rats. They were anesthetized with ketamine (120 mg/kg, i.p.) and their lungs were mechanically ventilated. Intravenous administration of fentanyl (100 μg/kg) consistently evoked a significant increase in the electromyographic activity (EMG) recorded from the sacrococcygeus dorsalis lateralis muscle. This implied muscular rigidity was appreciably attenuated by intracerebroventricular administration of NPY (4 nmol/2.5 μl). Microinjection of NPY (40 or 160 pmol/50 nl) into the bilateral locus coeruleus (LC) elicited an inhibition of the EMG activation induced by fentanyl in a dose-dependent manner. Microinjection of 160 pmol NPY plus antiserum against NPY (NPY Ab, 1:20) into the LC failed to suppress fentanyl-induced muscular rigidity. However, this implied muscular rigidity was not affected by NPY plus normal rabbit serum (NRS, 1:20). In addition, NPY Ab or NRS per se had no substantial effect on the rigidity. Microinjection of NPY (160 pmol) into the areas adjacent to the LC did not attenuate the rigidity. Our results suggest that the centrally administered NPY attenuated fentanyl-induced muscular rigidity by acting at the LC, but endogenous NPY may not be involved in this process.

Activation of central neuropeptide Y Y1 receptors potently stimulates food intake in male rhesus monkeys.

The orexigenic role of central neuropeptide Y (NPY) in nonhuman primates has been questioned. Therefore, we have studied the effect of central NPY on feeding in ad libitum-fed male rhesus macaques. NPY dose-dependently increased food intake, with the maximal effect obtained by 50 microg (960 min food intake +/- SEM, 104 +/- 5 to 188 +/- 11 g; vehicle vs. NPY; n = 6). Blood glucose levels were unaffected by intracerebroventricular administration of NPY, but animals receiving either 20 or 50 microg displayed increased plasma levels of insulin and cortisol at few time points. To assess the pharmacological specificity of this response, a novel Y1 antagonist, [(Ile,Glu,Pro,Daba,Tyr,Arg,Leu,Arg,Tyr-NH2)2 cyclic (2,4'),(2',4)-diamide] (Y1ANT), was synthesized. Receptor binding experiments demonstrated that Y1ANT preferentially binds to Y1 and Y4 receptors (pKi 10.12 +/- 0.06 and 9.11 +/- 0.05 nmol/L, respectively). Functional analysis revealed that Y1ANT is a Y1 antagonist and a partial Y4 agonist. Central administration of Y1ANT blocked NPY-induced feeding. In food-deprived monkeys, Y1ANT attenuated the feeding response. However, Y1ANT had no effect on food intake in satiated monkeys. Thus, endogenous NPY is likely to be involved in the regulation of food intake in the nonhuman primate, and this effect is at least partially mediated via Y1-like receptors.

Interactions between leptin and hypothalamic neuropeptide Y neurons in the control of food intake and energy homeostasis in the rat.

Leptin acts on the brain to inhibit feeding, increase thermogenesis, and decrease body weight. Neuropeptide Y (NPY)-ergic neurons of the hypothalamic arcuate nucleus (ARC) that project to the paraventricular nuclei (PVN) and dorsomedial nuclei (DMH) are postulated to control energy balance by stimulating feeding and inhibiting thermogenesis, especially under conditions of energy deficit. We investigated whether leptin's short-term effects on energy balance are mediated by inhibition of the NPY neurons. Recombinant murine leptin (11 microg) injected into the lateral ventricle of fasted adult Wistar rats inhibited food intake by 20-25% between 2 and 6 h after administration, compared with saline-treated controls (P < 0.05). Uncoupling protein mRNA levels in brown adipose tissue (BAT) rose by 70% (P < 0.01). Leptin treatment significantly reduced NPY concentrations by 20-50% (P < 0.05) in the ARC, PVN, and DMH and significantly decreased hypothalamic NPY mRNA levels (0.61 +/- 0.02 vs. 0.78 +/- 0.03 arbitrary units; P < 0.01). A second study examined changes in leptin during 5 days' intracerebroventricular NPY administration (10 microg/day), which induced sustained hyperphagia and excessive weight gain. In NPY-treated rats, leptin mRNA levels in epididymal fat were comparable to those in saline-treated controls (0.94 +/- 0.17 vs. 1.0 +/- 0.28 arbitrary units; P > 0.1), but plasma leptin levels were significantly higher (4.88 +/- 0.66 vs. 2.85 +/- 0.20 ng/ml; P < 0.01). Leptin therefore acts centrally to decrease NPY synthesis and NPY levels in the ARC-PVN projection; reduced NPY release in the PVN may mediate leptin's hypophagic and thermogenic actions. Conversely, NPY-induced obesity results in raised circulating leptin concentrations. Leptin and the NPY-ergic ARC-PVN neurons may interact in a homeostatic loop to regulate body fat mass and energy balance.

Induction and reversibility of an obesity syndrome by intracerebroventricular neuropeptide Y administration to normal rats

Intracerebroventricular neuropeptide Y (NPY) administration to normal rats for 7 days produced a sustained, threefold increase in food intake, resulting in a body weight gain of more than 40 g. Basal plasma insulin and triglyceride levels were increased in NPY-treated compared to vehicle-infused rats by about four- and two-fold, respectively. The glucose utilization index of white adipose tissue, measured by the labelled 2-deoxy-d-glucose technique was four times higher in NPY-treated rats compared to controls. This change was accompanied by an increase in the insulin responsive glucose transporter protein (GLUT 4). In marked contrast, muscle glucose utilization was decreased in NPY-treated compared to vehicle-infused animals. This change was accompanied by an increase in triglyceride content. When NPY-treated rats were prevented from overeating, there was no decrease in muscle glucose uptake, nor was there an increase in muscle triglyceride content. This suggests that muscle insulin resistance of ad libitum-fed NPY-treated rats is due to a glucose-fatty acid (Randle) cycle. When intracerebro-ventricular NPY administration was stopped and rats kept without any treatment for 7 additional days, all the abnormalities brought about by the neuropeptide were normalized. A tonic central effect of NPY is therefore needed to elicit and maintain most of the hormonal and metabolic abnormalities observed in the present study. Such abnormalities are analogous to those seen in the dynamic phase of obesity syndromes in which high hypothalamic NPY levels have been reported.

Chronic intracerebroventricular neuropeptide-Y administration to normal rats mimics hormonal and metabolic changes of obesity

Chronic intracerebroventricular neuropeptide-Y administration to normal rats mimics hormonal and metabolic changes of obesity

Role of neuropeptide-Y in episodic luteinizing hormone release in ovariectomized rats: an excitatory component and opioid involvement.

We tested the hypothesis that hypothalamic neuropeptide-Y (NPY) is an excitatory signal in the episodic secretion of LH in ovariectomized (ovx) rats and that the suppression of LH secretion that consistently follows intracerebroventricular administration of NPY is due to concurrent release of opioids or CRH, both previously shown to readily inhibit LH release. In the first experiment, ovx rats received continuous intraventricular infusion of either serum containing NPY antibodies (NPY-Ab) or normal rabbit serum (control) at dilutions of 1:5 or 1:1. NPY-Ab infusion at a 1:5 dilution significantly decreased mean plasma LH levels and LH pulse amplitude without affecting LH pulse frequency over a 3-h period of observation. However, infusion of relatively more concentrated NPY-Ab (1:1) markedly decreased not only mean plasma LH levels and LH pulse amplitude, but also the frequency of LH episodes. In the next experiment, we observed that intraventricular administration of NPY (0.2 nmol) suppressed LH release for 60 min. However, blockade of opiate receptors with iv infusion of naloxone (2 mg/h) before and after NPY injection completely counteracted the NPY-induced inhibition of LH release. On the other hand, prior blockade of the CRH receptors with alpha-helical CRH-(9-41) (25 or 100 micrograms/rat) was ineffective in reversing the inhibitory LH response of NPY (0.125 nmol). These results together with our previous demonstration of morphological communication between NPY and beta-endorphin neurons, show that suppression of LH by exogenous NPY in ovx rats may result from concurrent stimulation of opioids, primarily beta-endorphin. However, diminution of all parameters of episodic LH secretion by NPY-Ab affirms the notion that the NPY network is a physiologically important excitatory component of the hypothalamic pulse generator circuitry that regulates episodic LH secretion in rats.

Role of neuropeptide-Y in episodic luteinizing hormone release in ovariectomized rats: an excitatory component and opioid involvement

We tested the hypothesis that hypothalamic neuropeptide-Y (NPY) is an excitatory signal in the episodic secretion of LH in ovariectomized (ovx) rats and that the suppression of LH secretion that consistently follows intracerebroventricular administration of NPY is due to concurrent release of opioids or CRH, both previously shown to readily inhibit LH release. In the first experiment, ovx rats received continuous intraventricular infusion of either serum containing NPY antibodies (NPY-Ab) or normal rabbit serum (control) at dilutions of 1:5 or 1:1. NPY-Ab infusion at a 1:5 dilution significantly decreased mean plasma LH levels and LH pulse amplitude without affecting LH pulse frequency over a 3-h period of observation. However, infusion of relatively more concentrated NPY-Ab (1:1) markedly decreased not only mean plasma LH levels and LH pulse amplitude, but also the frequency of LH episodes. In the next experiment, we observed that intraventricular administration of NPY (0.2 nmol) suppressed LH release for 60 min. However, blockade of opiate receptors with iv infusion of naloxone (2 mg/h) before and after NPY injection completely counteracted the NPY-induced inhibition of LH release. On the other hand, prior blockade of the CRH receptors with alpha-helical CRH-(9-41) (25 or 100 micrograms/rat) was ineffective in reversing the inhibitory LH response of NPY (0.125 nmol). These results together with our previous demonstration of morphological communication between NPY and beta-endorphin neurons, show that suppression of LH by exogenous NPY in ovx rats may result from concurrent stimulation of opioids, primarily beta-endorphin. However, diminution of all parameters of episodic LH secretion by NPY-Ab affirms the notion that the NPY network is a physiologically important excitatory component of the hypothalamic pulse generator circuitry that regulates episodic LH secretion in rats.

Centrally administered NPY stimulated gastric acid and pepsin secretion by a vagally mediated mechanism

We investigated the possible roles of centrally administered neuropeptide Y (NPY) on gastric secretion, serum gastrin levels and gastric mucosal blood flow in anesthetized rats. Centrally administered NPY dose-dependently stimulated gastric acid and pepsin secretion. The stimulatory effect of intracerebroventricular administration of NPY was more potent than that of intracisternal administration. Centrally administered NPY also increased gastric secretion in the central noradrenaline depleted rats. In contrast, intravenously administered NPY had no influence on gastric secretion. These stimulatory effects were abolished by vagotomy or atropine pretreatment. The serum gastrin levels did not change after central NPY injection. Although intravenously administered NPY slightly increased gastric mucosal blood flow, centrally administered NPY slightly diminished gastric mucosal blood flow. These results indicate that centrally administered NPY markedly influences gastric functions in the rat.

Inhibitory effects of neuropeptide Y (NPY) on CRF and stress-induced cecal motor response in rats

The effects of NPY on CRF and stress-stimulated cecal motility were investigated by electromyography in rats. Intracerebroventricular (ICV) injection of NPY at 300 ng/kg significantly reduced the frequency of spike burst during the first 15 minutes after its administration while no effects was observed at a lower dose (150 ng/kg). Exposure to mental stress (MS) increased significantly (p<0.01) during 45 minutes, the frequency of cecal spike bursts. NPY (300 ng/kg) injected ICV, 30 minutes prior to MS periods abolished the excitatory effects induced by stress. The frequency of cecal spike bursts was also increased during the first 15-minutes following ICV injection of CRF (300 ng/kg). Prior (5 min) ICV administration of NPY (150 ng/kg) abolished the stimulatory effect of CRF on cecal motility. It is concluded that central administration of NPY suppresses the stress-induced cecal motor response probably by inhibiting the pathways involved in CRF mediation of these effects.

Effects of central and peripheral neuropeptide Y on sodium and water excretion in the rat

Neuropeptide Y (NPY) is widely distributed throughout the central nervous system and in several sympathetically innervated tissues, including the kidney. Although many central and peripheral acting endogenous compounds alter renal function, the role of NPY is unknown. Accordingly, we examined the effects of intracerebroventricular (ICV) or intrarenal administration of NPY on sodium and water excretion in the barbiturate anesthetized rat. Sprague-Dawley rats were uninephrectomized 10 days prior to testing and, in rats undergoing ICV administration, cannulae were implanted 3 days prior to testing. For testing, rats were anesthetized (Nembutal) and the jugular vein, renal artery and ureter catheterized. The results showed that the intrarenal infusion of NPY at 1 μg/kg/min increased sodium and water excretion relative to the saline control group without altering blood pressure or creatinine clearance. Similarly, ICV administration of NPY at 10 μg in a 5 μl volume increased the excretion of sodium and water without altering blood pressure as compared to the artificial CSF group. These findings suggest that both central and peripheral NPY may contribute to the regulation of sodium and water excretion in the rat.