Effect of intracerebroventricular alpha-MSH on food intake, adiposity, c-Fos induction, and neuropeptide expression

alpha-Melanocyte-stimulating hormone (alpha-MSH) is a hypothalamic neuropep tide proposed to play a key role in energy homeostasis. To investigate the behavioral, metabolic, and hypothalamic responses to chronic central alpha- MSH administration, alpha-MSH was infused continuously into the third cereb ral ventricle of rats for 6 days. Chronic alpha-MSH infusion reduced cumula tive food intake by 10.7% (P< 0.05 vs. saline) and body weight by 4.3% (P< 0.01 vs. saline), which in turn lowered plasma insulin levels by 29.3% (P< 0.05 vs. saline). However, alpha-MSH did not cause adipose-specific wasting nor did it alter hypothalamic neuropeptide mRNA levels. Central alpha-MSH infusion acutely activated neurons in forebrain areas such as the hypothala mic paraventricular nucleus, as measured by a 254% increase in c-Fos-like i mmunoreactivity (P< 0.01 vs. saline), as well as satiety pathways in the hi ndbrain. Our findings suggest that, although an increase of central melanoc ortin receptor signaling acutely reduces food intake and body weight, its a norectic potency wanes during chronic infusion and causes only a modest dec rease of body weight.