Hypothalamic galanin is up-regulated during hyperphagia and increased bodyweight gain induced by disruption of signaling in the ventromedial nucleus

Disruption of signaling in the ventromedial nucleus (VMN) by colchicine (CO L) produces transient (4 days) hyperphagia and weight gain. Microinjection of galanin into various hypothalamic sites stimulates feeding, so we tested the hypothesis that galanin is up-regulated in COL-treated rats by analyzi ng galanin concentrations in micropunched hypothalamic sites. Galanin was i ncreased in the paraventricular nucleus on Days 1 through 4 after COL-injec tion. Galanin was also elevated in three other hypothalamic sites, the dors omedial nucleus, lateral hypothalamic area, and perifornical hypothalamus, on Days 2-4 and in the lateral preoptic area, on Day 1 only. In the median eminence-arcuate nucleus and amygdala an initial decrease on Day 1 was foll owed by a then progressive increase through Day 4. These increases occurred despite marked elevations in blood insulin and leptin, hormones known to s uppress hypothalamic galanin. When COL- or saline-treated rats were injecte d intracerebroventricularly with galanin, it stimulated feeding further in the hyperphagic COL-treated rats, but the relative response over basal cons umption was similar in both COL-treated and control rats. These results in VMN disrupted rats suggest that neurochemical rearrangements, including inc reased availability of galanin, may contribute to the hyperphagia and incre ased weight gain; additionally, it seems that neurons in the VMN normally e xert a restraint on galanin signaling. (C) 2000 Elsevier Science Inc. All r ights reserved.