CHRONIC DELIVERY OF alpha-MELANOCYTE-STIMULATING HORMONE IN RAT HYPOTHALAMUS USING ALBUMIN-ALGINATE MICROPARTICLES: EFFECTS ON FOOD INTAKE AND BODY WEIGHT

摘要

Chronic delivery of neuropeptides in the brain is a useful experimental approach to study their long-term effects on various biological parameters. In this work, we tested albumin-alginate microparticles, as a potential delivery system, to study if continuous release in the hypothalamus of alpha-melanocyte-stimulating hormone (alpha-MSH), an anorexigenic neuropeptide, may result in a long-term decrease in food intake and body weight. The 2-week release of alpha-MSH from peptide-loaded particles was confirmed by an in vitro assay. Then, daily food intake and body weight were studied for 18 days in rats injected bilaterally into the paraventricular hypothalamic nucleus with particles loaded or not with alpha-MSH. A decrease in body weight gain, persisting throughout the study, was found in rats injected with alpha-MSH-charged particles as compared with rats receiving non-charged particles and with rats injected with the same dose of alpha-MSH in solution. Food intake was significantly decreased for 3 days in rats receiving alpha-MSH-loaded particles and it was not followed by the feeding rebound effect which appears after food restriction. The presence of alpha-MSH-loaded particles in the hypothalamus was confirmed by immunohistochemistry. In conclusion, our study validates albumin-alginate microparticles as a new carrier system for long-term delivery of neuropeptides in the brain and demonstrates that chronic delivery of alpha-MSH in the hypothalamus results in a prolonged suppression of food intake and a decrease of body weight gain in rats. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.