NALTREXONE INDUCES ARCUATE NUCLEUS NEUROPEPTIDE-Y GENE-EXPRESSION IN THE RAT

Neuropeptide Y (NPY) has potent effects on several components of energ y metabolism, including increased feeding and decreased brown fat ther mogenesis. Negative energy balance, such as food deprivation, increase s NPY mRNA in hypothalamic arcuate nucleus (ARC). Naltrexone (NLTX), a n opioid receptor antagonist, decreases NPY-induced feeding. We hypoth esized that NLTX would alter ARC NPY mRNA and change NPY effects on br own fat. Osmotic minipumps prefilled with either saline or NLTX (70 mu g/h) were implanted subcutaneously in 32 male Sprague-Dawley rats. On e-half of the rats were food deprived and one-half were allowed food a d libitum for 48 h. Food intake was measured at 24 and 48 h. At 48 h, ARC NPY mRNA and brown fat uncoupling protein (UCP) mRNA levels were d etermined using cDNA probes. Forty-eight-hour food intake was signific antly decreased by 24% after NLTX infusion. Food deprivation and NLTX treatment significantly and independently increased ARC NPY mRNA and d ecreased UCP mRNA levels in brown fat, suggesting a complex interactio n between hypothalamic NPY and endogenous opioids in the regulation of energy balance.