Neuropeptide Y Stimulates Feeding but Inhibits Sexual Behavior in Rats*

Abstract

The effects of neuropeptide Y (NPY), a tyrosine-rich peptide found in the rat brain, on feeding and sexual behavior were studied in male and female rats. Intraventricular (ivt) injections of NPY during the final hours of the light period induced feeding in a dose-related manner. While the lowest dose tested (0.02 nM) was without effect, higher doses (0.12, 0.47, 2.3 nM) uniformly elicited feeding with a latency of about 15 min in male rats. With the most effective dose, 0.47 nM, the increased food intake was due to an increased local eating rate. In contrast, the pattern of feeding behavior after a related peptide, rat pancreatic polypeptide (rPP), was quite different and less impressive. During the first hour, only one ivt dose of rPP (0.45 nM) evoked an increase in food intake, due to an increased time spent eating. Further, the effects of NPY on food intake were greater during the nocturnal period. Interestingly, increased food intake in nocturnal tests (4 h) was due solely to augmented intake during the first 60 min after ivt administration.In mating tests, initiated 2 h after the onset of darkness and 10 min after ivt administration of peptide, all but the lowest dose of NPY (0.01 nM) drastically suppressed ejaculatory behavior. Most rats treated with higher doses of NPY (0.02, 0.12, or 0.47 nM) mounted and intromitted only a few times before the cessation of sexual activity, and elongated latencies to the initial mount and intromission were observed. In contrast to the dramatic NPY-induced suppression of ejaculatory behavior, rPP (0.11 and 0.45 nM) was without effect on copulatory behavior. To substantiate further that the impairment of sexual behavior seen in NPY-treated rats was not due to an attenuated sexual ability, an additional experiment was performed. Penile reflexes, including erection, were monitored 10 min after ivt injection of NPY (0.12 nM), rPP (0.11 nM), or saline. No effect of NPY or rPP was observed on the proportion of rats showing erection or latency to initial erection, or in the number of erections per test. In fact, a slight facilitation of penile dorsiflexion responses was seen after NPY. These findings suggest that NPY selectively depresses sexual motivation in the male rat.In ovariectomized female rats responding to estrogen plus progesterone with a good level of sexual receptivity (lordosis quotient > 70), ivt saline and 0.01 nM NPY were without effect on sexual behavior. However, higher doses of NPY (0.12 and 0.47 nM) promptly suppressed sexual behavior in tests initiated 10 min after treatment. A significant 50% decrement in receptivity and a virtual elimination of proceptive behavior were observed. Further, although a low level of mounting (one to five mounts in 15 min) was seen in both the saline (33% mounting) and the 0.01 nM NPY (38% mounting) treated groups, none was observed in animals treated with the higher NPY doses. These observations indicate that NPY may also suppress female sexual behavior.These studies demonstrate that NPY, a novel hypothalamic peptide, st...

Novel analogues of neuropeptide Y with a preference for the Y1‐receptor

“…Only [Arg6,Pro34]pNPY (8) showed a fivefold loss in efficacy owing to an increase in binding. A 10-fold loss in affinity, but almost equal efficacy was found for [cPP20±23, Pro34]pNPY (2), whereas similar affinity in binding and inhibition of cAMP production was found for [Phe7, Pro34]pNPY (11).…”

“…Profound effects on stimulation of food intake, secretion of luteinizing and growth hormone, and insulin release suggest an important role for NPY in the pathophysiology of obesity and diabetes [2±5]. A wide range of other effects of NPY have been reported, such as potent vasoconstriction [6], facilitation of learning and memory [7], modulation of locomotor behaviours [8], induction of hypothermia [9,10], inhibition of sexual behaviour [11], shifts in circadian rhythms [12], modulation of cardiorespiratory parameters[13], anxiolytic potency [14] and inhibition of alcohol consumption and resistance [15].NPY is a 36-amino acid peptide amide belonging to the family of pancreatic polypeptides that includes also pancreatic polypeptide (PP) and peptide YY; it was first isolated from pig brain in 1982 [16].NPY is widely distributed within the central nervous system and in the periphery. [25,26].…”

The Neuropeptide Y (NPY) Y1 Receptor Subtype Mediates NPY-induced Antidepressant-like Activity in the Mouse Forced Swimming Test

“…Intracerebroventricular (ICV) administration of NPY stimulates food intake (Clark et al 1985;Levine and Morley 1984;Stanley and Leibowitz 1984), modulates cognition (Flood et al 1987;Redrobe et al 1999), inhibits neuronal excitability (Colmers and Bleakman 1994) and has anticonvulsant effects (Vezzani et al 1999). NPY modulates the secretion of various hypothalamic neuropeptides, stimulates the corticotrophic axis (Krysiak et al 1999;Small et al 1997) and has potent inhibitory effects on gonadotrophic and somatotrophic axes (Catzeflis et al 1993).…”

Inhibitory effects of central neuropeptide Y on the somatotropic and gonadotropic axes in male rats are independent of adrenal hormones

“…The obesity syndrome which results from chronically elevated hypothalamic NPY levels in rodents [3,28,30,33,40,46,47] is still present even when NPY--induced hyperphagia is prevented [3,30,46], demonstrating that hyperphagia is not necessary for central NPY to produce its obesity--like effects. NPY in the hypothalamus is also involved in the regulation of several other important physiological processes including growth [4,22,25], reproduction [4,5,25], and fluid balance [13]. For example, intracerebroventricular (ICV) administration of NPY to rats has been shown to inhibit the somatotropic axis by reducing the pituitary content of growth hormone (GH) [4], abolishing the normal pulsate release of GH into the plasma [25], and consequently reducing the plasma concentrations of GH and its main effector in the periphery insulin--like growth factor I (IGF--1) [4,22,25].…”

“…For example, intracerebroventricular (ICV) administration of NPY to rats has been shown to inhibit the somatotropic axis by reducing the pituitary content of growth hormone (GH) [4], abolishing the normal pulsate release of GH into the plasma [25], and consequently reducing the plasma concentrations of GH and its main effector in the periphery insulin--like growth factor I (IGF--1) [4,22,25]. Centrally infused NPY was also shown to inhibit several parameters of the gonadotropic axis of both male and female intact rats, such as the reduction of plasma sex hormone levels, resulting in reduced gonadal weight and impaired sexual function [4,5,25]. The diverse roles of NPY are mediated by several different Y--receptor subtypes, five of which have been cloned to date (Y1, Y2, Y4, Y5 and Y6).…”