EFFECT OF HYPOTHALAMIC ADMINISTRATION OF GROWTH HORMONE-RELEASING FACTOR (GRF) ON FEEDING-BEHAVIOR IN RATS

To examine the role and working site of growth hormone-releasing factor (GRF) in feeding behavior, we first tested the effect of the intracerebroventricular (i.c.v.) injection of GRF on food intake after 24 h of food deprivation. Cumulative food intake was measured 1, 3 and 6 h after injection. A lower dose of GRF stimulated food intake in a dose dependent manner (3 h; GRF 100 pmol 8.64 +/- 1.06 g vs saline 5.50 +/- 0.60 g, P < 0.05), while a higher dose (1 nmol, 500 pmol) suppressed food intake (3 h; GRF 1 nmol 2.65 +/- 0.70 g vs saline 5.50 +/- 0.60 g, P < 0.01). Second, the effect of i.c.v. injection of 100 pmol of GRF on peripheral metabolites was examined. The subsequent levels of plasma insulin, glucagon, glucose and non-esterified fatty acid showed no significant difference from those of saline administration. Third, the effect of microinjection of GRF (5 pmol) into several hypothalamic areas on food intake was examined. Injection into the ventromedial hypothalamic nucleus (VMN) stimulated food intake (3 h; GRF 5 pmol 10.32 +/- 1.04 g vs saline 6.92 +/- 0.32 g, P < 0.05), but no significant effect was observed following injection either into the lateral hypothalamic area (LHA), paraventricular nucleus (PVN) or medical preoptic area (MPOA). Finally, we tested the stimulatory effect of GRF on food intake in bilateral VMN lesioned rats. I.c.v. injection in these animals had no more significant effect on food intake than did saline injection in VMN lesioned rats (3 h; GRF 100 pmol 6.27 +/- 0.87 g vs saline 5.34 +/- 0.44 g). These results suggest that administration of a low dose of GRF centrally enhances feeding behavior and that the VMN is one of the working sites of this effect.