Repeated intracerebroventricular administration of glucagon-like peptide-1-(7-36) amide or exendin-(9-39) alters body weight in the rat

Central nervous system glucagon-like peptide-1-(7-36) amide (GLP-1) adminis tration has been reported to acutely reduce food intake in the rat. We here report that repeated intracerebroventricular (icv) injection of GLP-1 or t he GLP-1 receptor antagonist, exendin-(9-39), affects food intake and body weight. Daily icy injection of 3 nmol GLP-1 to schedule-fed rats for 6 days caused a reduction in food intake and a decrease in body weight of 16 +/- 5 g (P < 0.02 compared with saline-injected controls). Daily icy administra tion of 30 nmol exendin-(9-39) to schedule-fed rats for 3 days caused an in crease in food intake and increased body weight by 7 +/- 2 g (P < 0.02 comp ared with saline-injected controls). Twice daily icy injections of 30 nmol exendin-(9-39) with 2.4 nmol neuropeptide Y to ad libitum-fed rats for 8 da ys increased food intake and increased body weight by 28 +/- 4 g compared w ith 14 +/- 3 g in neuropeptide Y-infected controls (P < 0.02). There was no evidence of tachyphylaxis in response to icy GLP-1 or exendin-(9-39). GLP- 1 may thus be involved in the regulation of body weight in the rat.