Involvement of neuropeptide Y Y1 receptors in the acute, chronic and withdrawal effects of nicotine on feeding and body weight in rats

Abstract

We investigated the role of neuropeptide Y Y1 receptors in acute, chronic and withdrawal effects of nicotine with reference to feeding behavior. Rats were administered with nicotine, neuropeptide Y, neuropeptide Y Y1 receptor agonist [Leu31,Pro34]neuropeptide Y or antagonist BIBP3226 (N2-diphenylacetyl)-N-[(4-hydroxy-phenyl)-methyl]-d-arginine amide) via i.c.v. route, and food intake was measured at 2 and 6 h post-injection time-points. While acute nicotine or BIBP3226 reduced food intake, increase was observed following neuropeptide Y or [Leu31,Pro34]neuropeptide Y. Nicotine-induced anorexia was antagonized by pre-treatment with neuropeptide Y or [Leu31,Pro34]neuropeptide Y, and potentiated by BIBP3226. Furthermore, effects of chronic nicotine (i.p.) and its withdrawal, alone and in combination with BIBP3226 were evaluated with reference to feeding and body weight. Concurrent administration of BIBP3226 with nicotine prevented the development of tolerance to nicotine-induced anorexia, and withdrawal hyperphagia and weight gain. Moreover, acute BIBP3226 attenuated the hyperphagia following nicotine termination. Additionally, immunocytochemical profile of neuropeptide Y in the hypothalamus was studied following differential nicotine treatments. Acute nicotine treatment dramatically reduced neuropeptide Y immunoreactivity in the arcuate and paraventricular nuclei. Chronic nicotine administration decreased neuropeptide Y immunoreactivity in arcuate, but not in paraventricular nucleus. Nicotine withdrawal resulted in significant increase in the neuropeptide Y immunoreactivity in both the nuclei. Neuropeptide Y immunoreactivity in the lateral hypothalamus did not change following any of the treatments. The results suggest that neuropeptide Y in the arcuate and paraventricular nuclei of hypothalamus may be involved in acute, chronic and withdrawal effects of nicotine on the feeding behavior, possibly via neuropeptide Y Y1 receptors.