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

Abstract

Disruption of signaling in the ventromedial nucleus (VMN) by colchicine (COL) 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 analyzing galanin concentrations in micropunched hypothalamic sites. Galanin was increased in the paraventricular nucleus on Days 1 through 4 after COL-injection. Galanin was also elevated in three other hypothalamic sites, the dorsomedial 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 followed by a then progressive increase through Day 4. These increases occurred despite marked elevations in blood insulin and leptin, hormones known to suppress hypothalamic galanin. When COL- or saline-treated rats were injected intracerebroventricularly with galanin, it stimulated feeding further in the hyperphagic COL-treated rats, but the relative response over basal consumption was similar in both COL-treated and control rats. These results in VMN disrupted rats suggest that neurochemical rearrangements, including increased availability of galanin, may contribute to the hyperphagia and increased weight gain; additionally, it seems that neurons in the VMN normally exert a restraint on galanin signaling.