Injection Of Neuropeptide Y Research Articles

Chronic administration of neuropeptide Y into the lateral ventricle starting at 30 days of life delays sexual maturation in the female rat.

The role of neuropeptide Y (NPY) in the regulation of sexual function is still controversial. Whereas central NPY administration is stimulatory during proestrus in the rat and other species, such administration is inhibitory in castrated animals and we have shown that chronic, central infusion of NPY inhibits both the gonadotropic and somatotropic axis in adult rats. Previous studies have suggested that NPY could be involved in the triggering of the first ovulatory LH surge and a recent report indicated that a single central NPY injection given at 30 days of life could advance sexual maturation. We therefore evaluated the effect of chronic NPY administration on the timing of sexual maturation in the female rat and compared the effects obtained with those induced by a single NPY injection. Constant infusion of NPY (18 micrograms/day) into the lateral ventricle delayed sexual maturation as seen by the absence of vaginal opening, delayed ovarian growth and reduced number of pituitary GnRH receptors. This inhibitory effect was seen as long as NPY was infused. In contrast, a single NPY injection either at 30 days of life or earlier, or repeated single injections between 28 and 31 days of life, did not modify the pace of sexual maturation. Unlike what is observed in adult animals, overall food intake was only minimally increased between 30 and 37 days of life in chronically NPY-infused rats, but this increase became more important thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of Neuropeptide Y in the Regulation of Tyrosine Hydroxylase Messenger Ribonucleic Acid Levels in the Male Rat Arcuate Nucleus as Evaluated by in situ Hybridization

Neuroanatomical data have clearly demonstrated the existence of synaptic contacts between neuropeptide Y (NPY) endings and tuberoinfundibular dopaminergic (TIDA) neurons in the rat arcuate nucleus. In order to determine the influence of NPY in the biosynthesis of dopamine, we have studied the effects of NPY and some NPY analogs on tyrosine hydroxylase (TH) gene expression in TIDA neurons in the male rat. The following peptides: NPY, PYY, [Leu31, Pro34]-NPY (a Y1 receptor agonist) and NPY13-36 (a Y2 receptor agonist) were injected into the left lateral ventricle of adult male rats. All the animals were perfused with 4% paraformaldehyde 4 h after injection. Cryostat sections through the arcuate nucleus were processed for quantitative in situ hybridization. The intracerebroventricular injection of NPY, PYY and [Leu31, Pro34]-NPY induced an increased of 43, 33 and 42%, respectively, in the number of grains overlying TH neurons. On the other hand, the Y2 receptor agonist NPY13-36 did not influence mRNA levels. These data then strongly suggest that NPY positively regulates the genetic expression of TH in rat TIDA neurons via the Y1 NPY receptor subtype.

The pseudo-affective reflex of pagani-sherrington as screening test for serotoninergic drugs

The feeding effects of 5-hydroxytryptamine (5-HT)1 and 5-HT2 receptor agonists injected into the hypothalamic paraventricular nucleus (PVN) immediately prior to PVN administration of neuropeptide Y (NPY) were examined. The impact of these same compounds on NPY-induced alterations in energy metabolism was also assessed in an attempt to characterize further the potential interactive relationship of PVN NPY and 5-HT on feeding and whole body calorimetry. Specifically, several experiments examined the effect of various 5-HT receptor agonists on NPY-stimulated eating and alterations in energy substrate utilization [respiratory quotient (RQ)]. This included the 5-HT1A receptor agonist 8-OH-DPAT, the 5-HT1B/1A agonist RU 24969, the 5-HT1D agonist L-694,247, the 5-HT2A/2C agonist DOI, the 5-HT2B agonist BW 723C86 and the 5-HT2C agonist mCPP. In feeding tests conducted at the onset of the dark cycle, drugs were administered 5 min prior to PVN injection of NPY and food intake was measured 2 h postinjection. The metabolic effects of NPY following a similar pretreatment were monitored using an open-circuit calorimeter measuring the volume of oxygen consumed (VO2), carbon dioxide produced (VCO2) and RQ (VCO2/VO2). PVN injection of NPY (100 pmol) potentiated feeding and evoked reliable increases in RQ. Only DOI (2.5–5 nmol) pretreatment antagonized NPY-induced eating and blocked the peptide's effect on energy substrate utilization. Direct PVN pretreatment with spiperone (SPRN), a 5-HT2A receptor antagonist, and ketanserin (KTSN), a 5-HT2A/2C antagonist, but not SDZ SER 082, a 5-HT2B/2C antagonist, or the 5-HT2C antagonist RS 102221, blocked the effect of DOI in both feeding and metabolic tests providing additional evidence that activation of PVN 5-HT2A receptors inhibits NPY's action on feeding and substrate utilization.

Dissociated feeding and hypothermic effects of neuropeptide Y in the paraventricular and perifornical hypothalamus.

The present study investigated the effects of neuropeptide Y (NPY) on food intake and body temperature (Tbo) in free-feeding unrestrained rats following injection into the medial hypothalamic paraventricular nucleus (PVN) or the lateral perifornical hypothalamus (PFH). NPY (78-235 pmol) or saline was infused unilaterally into the PVN or PFH in a volume of 0.4 microliter and simultaneous measures of food intake and Tbo were taken every 30 min for 3 h. Results indicated that NPY evoked changes in eating behavior and Tbo that were dependent upon the site of hypothalamic injection. Although PVN and PFH administration of NPY both increased food intake dose dependently within 30 min of treatment, PFH NPY-injected rats (n = 9) showed a stronger behavioral response compared to rats (n = 9) receiving NPY injections into the PVN. In PVN-treated rats, however, the increased eating was associated with a significant decline in Tbo evident within the first 30-min test interval. A mean maximal decline of 0.92 +/- 0.26 degree C occurred within 90 min of PVN treatment of the highest dose, which produced a reduction in Tbo that was maintained for 2.5 h. In contrast, NPY infusion into the PFH failed to reliably alter Tbo at any of the doses tested. These findings are consistent with evidence that NPY in the PVN and PFH may have distinct functions and suggest that although PFH NPY acts to stimulate a robust and relatively specific ingestive response, PVN NPY may participate in the complex integrative mechanisms responsible for the simultaneous regulation of feeding, thermoregulatory, and metabolic processes.

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.

Effects of neuropeptide Y on short-term memory

Neuropeptide Y (NPY) is a ubiquitous neuropeptide which may modulate several behavioral and physiological phenomena. Among other behavioral effects, NPY has been shown to enhance memory processes in mice. The current study employed a delayed conditional discrimination procedure to evaluate the effects of intracerebroventricular injections of NPY on short-term working memory. This conditional discrimination procedure assesses appropriate responding, based on a previously presented stimulus, after various delays have been imposed between the stimulus and the opportunity for a response. Delay values ranged from 0.01 s to 30 s. NPY decreased accuracy across delay values in a dose-dependent manner. The two highest doses of NPY (3.0 and 10.0 μg) significantly decreased accuracy. Doses lower than those used in the current study have shown facilitation of memory processes under avoidance procedures in mice. Intraperitoneal naloxone (3.0 mg/kg), an opioid antagonist, completely blocked NPY's memory degrading effects. Procedural differences may account for NPY-induced degradation of short-term working memory under delayed conditional discrimination and previous reports of NPY's enhancement of retention under shock avoidance procedures.

Neuropeptide Y: Intrastriatal injections produce contralateral circling that is blocked by a dopamine antagonist in rats

The brain is rich in neuropeptide Y (NPY) but its function is poorly understood. Previous studies have shown that intrastriatal injections of NPY stimulate dopamine (DA) release. In the present paper, behavioral studies evaluated the possibility that unilateral intrastriatal injections of NPY would produce contralateral circling that could be blocked by coinjection with a DA antagonist. Four experiments examined circling behavior in rats after unilateral intrastriatal microinjections (0.5 μl) of: 1) amphetamine alone; 2) amphetamine with the DA antagonist cis-flupenthixol; 3) NPY alone; and 4) NPY with cis-flupenthixol. Each experiment consisted of seven test sessions; the first and seventh were preceded by no injection, the second and sixth by a control injection (saline or cis-flupenthixol with saline) and the third, fourth, and fifth by drug injections. Animals were scored during two 5-min intervals of a 20-min test session that began with the central injection and placement in a circular arena (30 cm diam.). Results indicated that the 25.0- but not the 6.0- or 12.0-μg doses of amphetamine and the 0.10- but not the 0.01- or 1.0-μg doses of NPY produced contralateral circling. This directional bias was antagonized by cis-flupenthixol (20 μg in 0.5 μl) in the case of amphetamine and fully blocked in the case of NPY. Results raise the intriguing possibility that contralateral circling induced by unilateral intrastriatal NPY may be mediated by DA.

Effects of intraventricular administration of neuropeptide Y on feeding behavior in fasted female rats with ventromedial hypothalamic lesions

The role of ventromedial hypothalamic nucleus (VMN) in feeding behavior induced by central administration of porcine neuropeptide Y (NPY) in fasted female rats was investigated focusing on the effect of the intracerebro-ventricular (i.c.v.) injection of NPY on food intake in rats with VMN lesions after 24 h of food deprivation. Cumulative food intake was measured 1, 3 and 6 h after injection. In Exp. 1, the i.c.v. injection of NPY into intact rats stimulated food intake compared with the injection of saline 1 and 3 h after the injections in a dose dependent manner (1 h; NPY 1 μg, 3.29 ± 0.43, 2 μg, 4.64 ± 0.88, 5 μg, 5.15 ± 0.61 vs. saline 2.48 ± 0.42 g , P<0.05 in 2 and 5 μg). 5 μg of NPY significantly stimulated food intake 6 h later. In Exp. 2, i.c.v. injection of NPY (2 μg) in VMN-lesioned rats showed no significant effect on food intake compared with the injection of saline 3 weeks after VMN lesioning (1 h; NPY 2 μg, 2.46 ± 0.58 vs. saline 2.39 ± 0.12 g ). These results suggest that central administration of NPY enhances food intake in fasted female rats and that the VMN is one of the crucial sites of NPY induced feeding.

Neuropeptide Y attenuates satiety: evidence from a detailed analysis patterns ingestion

Centrally injected neuropeptide Y (NPY) is a potent stimulant of ingestive behavior capable of augmenting both food and fluid intake in fully satiated animals. To gain further insight into NPY's mechanism of action, we recorded patterns of licking behavior in rats drinking sweetened condensed milk solutions immediately after lateral ventricular injection of NPY (10 μg) or vehicle. In a separate study, we examined licking patterns after 23 h food deprivation (FD) that produced approximately the same total intake as NPY. Consistent with previous reports, we found NPY stimulated intake by increasing total ingestion time and total volume consumed during a 1-h test. Although NPY the number of bouts of licking and shortened pauses between bouts, it also decreased mean bout size, duration and within-bout lick rat (local rate). It had no significant effect on start latency or lick efficiency (licks/ml). Further analyses revealed that NPY attenuated satiety (reduced slope of lick-rate functions with session time) but had no significant effect on the beginning lick rate, a measure related to orosensory excitation. In contrast to NPY, FD increased both the beginning lick rate and individual bout size without changing either the mean number of bouts or the pause between bouts. In general, NPY stimulated an intermittent pattern of licking and delayed satiation whereas FD increased the initial rate of licking and the size of individual bouts without changing the basic licking pattern. The increase in initial lick rate suggests that FD, unlike NPY, enhances orosensory stimulation. These data compliment previous results showing that NPY increases the motivation to eat. In particular, the present data suggest that NPY also promotes ingestion by producing a distinctive pattern of ingestion and slowing the rate of satiation.

Thermoregulatory effect of intracerebral injections of neuropeptide Y in rats at different environmental temperatures

1. 1. In order to characterize the thermoregulatory actions of brain neuropeptide Y (NPY), the effects of intra-third ventricular (I3V) injection of NPY on temperatures of colon ( T co), brown adipose tissue ( T BAT) and tail skin ( T s) were observed at ambient temperatures ( T a) of 19 and 8°C. 2. 2. The injection of NPY in a dose of 8 mcg/100 g body wt evoked a fall of T co by about 2°C in both neutral and cold environments. NPY (4 and 8 mcg/100 g body wt) induced dose-dependent T co falls in rats at thermoneutral environment. The thermolytic reactions induced by I3V administration of NPY were associated with a fall in T BAT but no changes in I s were observed. 3. 3. The results suggest that NPY may mediate hypothermic response in neutral and cold environments mainly by its effects on the brown adipose tissues in the rat.

Evidence that neuropeptide Y and dopamine in the perifornical hypothalamus interact antagonistically in the control of food intake

Mapping studies have revealed that the perifornical hypothalamus (PFH) is a primary locus for both the feeding-stimulatory effect of neuropeptide Y (NPY) and the anorectic effect of catecholamines (CAs), suggesting that NPY and CAs may interact antagonistically there. To investigate this, the CA-releasing agent amphetamine (AMPH) was injected through indwelling guide cannulas into the PFH of satiated adult male rats 5 min prior to injection of NPY (78 pmol/0.3 μl) and food intake was measured 1, 2, and 4 h later. Amphetamine (50–200 nmol) dose-dependently reduced NPY feeding, usually eliminating it at the higher doses. The receptors mediating this effect were investigated by sequential injection of various CA antagonists, AMPH, and NPY into the PFH. Neither the α- nor β-adrenergic receptor antagonists phentolamine (100 nmol) or propranolol (200 nmol) signficantly affected AMPH suppression of NPY feeding. In contrast, the dopamine receptor antagonist haloperidol (5 nmol) abolished AMPH suppression of NPY feeding, suggesting that dopamine (DA) mediates the AMPH effect. To examine this, epinephrine (EPI, 50–200 nmol) and DA (25–200 nmol) were tested for suppression of NPY-induced feeding. While EPI had no significant effect, DA at the maximally effective dose (50 nmol) reduced the NPY feeding response by 36% or more. These findings provide convergent evidence for antagonistic interactions between endogenous DA and NPY in the control of eating behavior.

Glucocorticoid receptors in PVN: interactions with NE, NPY, and Gal in relation to feeding

Norepinephrine (NE) and neuropeptide Y (NPY) potentiate carbohydrate ingestion after injection into the paraventricular nucleus (PVN), whereas injection of galanin (Gal) potentiates fat intake. The present study examines the relation between these neurochemically induced feeding behaviors and the adrenal steroids acting locally within the PVN. Results demonstrate that PVN NE- and NPY-induced carbohydrate intake is abolished by adrenalectomy surgery (ADX) and by local PVN implants of the type II receptor antagonist RU-486. Carbohydrate intake in response to PVN NE or NPY injection is unaffected by the type I antagonist RU-28318. In contrast, the stimulatory effect of PVN Gal injection on fat intake is unchanged by surgical ADX or by PVN administration of RU-486 or RU-28318, suggesting that the stimulatory action of Gal on fat ingestion occurs independently of corticosterone (Cort) and of PVN type I or type II steroid receptors. It is concluded that endogenous Cort has a permissive effect on the carbohydrate feeding responses elicited by NE and NPY in the PVN and that this interaction is mediated by type II glucocorticoid receptors within this nucleus.

Effects of neuropeptide Y on ingestion of flavored solutions in nondeprived rats

Recent evidence suggests that in addition to altering energy balance, neuropeptide Y (NPY) may stimulate ingestive behavior by modifying the orosensory quality of ingested substances. The present experiments investigated the effect of intracerebroventricular administration of NPY (5 μg/5 μl) on ingestion of various flavored solutions in nondeprived rats. Experiment 1 examined the effects of NPY on ingestion of a range of concentrations of saline, sucrose, and saccharin solutions in single-bottle tests. Results indicated that NPY stimulates ingestion of both sucrose and saccharin solutions that are normally palatable. In Experiment 2, palatable sucrose solutions flavored with either orange or black cherry Kool-Aid® for separate training groups were selectively associated with NPY injection during single-bottle training sessions. Subsequent two-bottle preference tests showed a significant shift in preference toward the flavor paired with NPY during training. The results of these experiments extend previous findings by showing that NPY can stimulate ingestion of sweet solutions regardless of caloric value and may potentiate sweet taste preference via an associative mechanism.

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.

Functional impairment of hypothalamic corticotropin-releasing factor neurons with immunotargeted toxins enhances food intake induced by neuropeptide Y

Previous work has shown that administration of corticotropin-releasing factor (CRF) into the lateral ventricle antagonizes the orexigenic effect of neuropeptide Y (NPY), and central injection of CRF antagonist, α-helical CRF(9–41) enhanced NPY-induced food intake in satiated rats. The aim of the present study was to determine the effects of selective inactivation of hypothalamic CRF neurons on food intake induced by NPY injection and to delinate which hypothalamic nucleus is involved in this NPY/CRF interaction related to the regulation of food intake. Impairment of CRF neuron function by immunotargeting of a ricin A chain toxin with a monoclonal antibody to CRF (CRF-MAb) has been previously reported. Administration of CRF-MAb/toxins into the paraventricular nucleus (PVN) two weeks prior to testing produced markedly enhanced eating induced by injection of NPY into the same nucleus. This effect was accompanied by a 60% decrease in CRF content within the hypothalamus and a 43% decrease of CRF in the median eminence, a site of projection of CRF neurons from the PVN. In contrast, injection of CRF-MAb/toxins into the ventromedial nucleus of the hypothalamus (VMH) did not modify the feeding induced by NPY injection into this hypothalamic area. Systemic pretreatment with the synthetic glucocorticoid dexamethasone at a dose known to downregulate the levels of CRF in the PVN also enhanced the feeding induced by intra-PVN injection of NPY.This suggests that an equilibrium between CRF and NPY neuronal function within the PVN may play an important role in the regulation of food intake. This interactive mechanism may provide some partial explanation of the eating disorders related to stress, in particular anorexia nervosa.

Increased neuropeptide Y concentrations in specific hypothalamic nuclei of the rat following treatment with methysergide: Evidence that NPY may mediate serotonin's effects on food intake

Neuropeptide Y (NPY) is a potent central appetite stimulant found in hypothalamic neurons that have close anatomical associations with neurons containing serotonin, a powerful anorectic agent. To determine whether the two neurotransmitters interact functionally, we have studied the effects on regional hypothalamic NPY concentrations of acute and chronic administration of methysergide, a 5-HT1 BC/ serotonin receptor antagonist. Chronic methysergide treatment (10 mg/kg/day) was given by subcutaneously implanted osmotic minipumps ( n = 8). Acute effects of methysergide were determined 4 h after a single injection (10 mg/kg) in a separate group ( n = 8). Controls ( n = 8) had implanted minipumps delivering saline, and also received a saline injection 4 h before sacrifice. Food intake was significantly increased ( p < 0.01) by both acute and chronic methysergide treatment. In the chronically treated rats, NPY levels were significantly increased over controls in the arcuate nucleus (ARC; by 41%, p = 0.02) and paraventricular nucleus (PVN; by 40%, p < 0.01). Acute methysergide treatment also increased NPY concentrations in the ARC (by 81%, p < 0.01) and PVN (by 30%, p < 0.01). Methysergide administration, which stimulated feeding, therefore raised NPY concentrations in the ARC, where NPY is synthesized, and in the PVN, a major site of NPY release where NPY injection induces hyperphagia. These findings suggest that NPYergic and serotoninergic innervations in the hypothalamus interact to regulate food intake, and raise the possibility that increased NPY release may mediate the hyperphagic effect of serotoninergic 5-HT1 BC/ receptor blockade.

Anxiolytic-Like Action of Neuropeptide Y: Mediation by Y1 Receptors in Amygdala, and Dissociation from Food Intake Effects

Evidence from animal and human studies suggests that neuropeptide Y (NPY) may be a potent endogenous anxiolytic. The anatomic structures mediating this action of the peptide remain unknown. Furthermore, in addition to its anxiolytic-like effects, intracerebroventricular administration of NPY induces food intake through hypothalamic mechanisms, making the anxiolytic-like action of the peptide more difficult to interpret. The purpose of this study was to examine the anatomic substrate for the effects of NPY on anxiety, and to characterize the NPY receptors mediating these effects. Intracerebroventricular injection of NPY produced increased food intake in free-feeding animals, and dose-dependent anticonflict/anxiolytic-like effects in an established animal model of anxiety, the Geller-Seifter punished responding test. In contrast, microinjection of NPY into the central nucleus of the amygdala did not increase food intake in free-feeding animals, did not affect unpunished lever pressing for food, but did reproduce the anticonflict/anxiolytic-like effect with high potency. The selective NPY-Y1 agonist, p[Leu31,Pro34]NPY was approximately equipotent with native NPY in the conflict paradigm, and markedly more potent than the Y2 agonist, NPY13-36. Intrastriatal injections had no effect on conflict behavior. Thus, activation of Y1 receptors in the central nucleus of the amygdala produces effects similar to established anxiolytics without affecting food intake, suggesting that Y1-receptors in the amygdala may be a substrate for anxiolytic actions of NPY.

Lack of norepinephrine--neuropeptide Y interactions in the hypothalamic control of cardiovascular regulation in urethane-anesthetized rats.

Noradrenergic input to the hypothalamus is implicated in cardiovascular and behavioral regulation. The hypothalamus also contains high concentrations of neuropeptide Y (NPY), which often is colocalized in noradrenergic neurons. Systemically, NPY has been demonstrated to act synergistically with norepinephrine. Injections of concentrated solutions of NPY into the cerebral ventricles or hypothalamus have been found to alter ingestive behaviours, but the role of NPY in cardiovascular regulation is unknown. The objectives of this study were to determine if NPY injected directly into the hypothalamus elicits cardiovascular responses and (or) if the simultaneous administration of NPY with norepinephrine alters the cardiovascular responses elicited by norepinephrine alone. The hypothalamus of the urethane-anesthetized rat was mapped for heart rate and blood pressure responses to injections of one of the following: saline; NPY (1.9 or 0.6 pmol per injection site); norepinephrine (24, 81, or 243 nmol per injection site); or the combination of norepinephrine plus NPY. Site and drug selection were randomized. Injections of 0.25 microL were at 1.0 microL/min, bilaterally for bilateral structures and unilaterally for midline structures. Norepinephrine routinely elicited dose-dependent increases in blood pressure with latencies of approximately 1 min, which peaked by 3-5 min, accompanied or followed by tachycardia. Saline and NPY injections alone elicited no significant responses in any site. When NPY was injected together with norepinephrine, there were no significant alterations in cardiovascular variables except for attenuation of pressor responses when NPY was injected into the preoptic region and attenuation of tachycardia when NPY was injected into the caudal hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)

Feeding responses to perifornical hypothalamic injection of neuropeptide Y in relation to circadian rhythms of eating behavior

Hypothalamic injection of neuropeptide Y (NPY) can elicit eating in satiated rats, and the perifornical hypothalamus (PFH) is the site where this effect is most pronounced (48). Additionally, there is a well-documented circadian rhythm of spontaneous eating behavior. Our objective was to determine whether there are daily rhythms of sensitivity to NPY in the PFH that might contribute to this behavioral rhythm. To accomplish this, the effectiveness in eliciting eating of PFH injection of NPY was examined at six different time points in the light-dark cycle. Neuropeptide Y (78 pmol/10 nl) or vehicle (10 nl) were injected through chronically implanted guide cannulas into the PFH of satiated adult male rats and food intake was measured 1, 2, and 4 h later. In animals on 12-12 h light-dark cycles, these injections were given 1 h before and after the onset of the light and dark phases, and in the middle of these phases. Additionally, doseresponse effects of NPY were examined at two points: the first hour of both the dark and the light phases. The results show that NPY was effective at every time tested, and that the magnitude of the peptide-elicited intakes was primarily additive to the underlying patterns of spontaneous intake, with only a modest daily cycle of sensitivity to NPY. Consistent with this, NPY dosedependently increased intake in the early light and in the early dark, and the magnitude of these effects across doses was similar at these times. This suggests that the sensitivity of the PFH system mediating NPY eating exhibits only a modest daily cycle. Therefore, circadian rhythms in the sensitivity of this system are likely to make only a small contribution to circadian rhythms of spontaneous eating.