CENTRAL ACTIONS OF PEPTIDE AND NONPEPTIDE GROWTH-HORMONE SECRETAGOGUES IN THE RAT

Evidence for a central site of action of growth-hormone-releasing pept ide (GHRP-6) was sought by (1) counting the number of Fos-positive nuc lei within the brain following intracerebroventricular or intravenous injection of peptide and non-peptide GH secretagogues and (2) characte rizing the electrophysiological responses of neuroendocrine arcuate ne urones (recorded in vivo) following intravenous injection of GHRP-6. C onscious male rats were chronically implanted with intracerebroventric ular or intravenous catheters. Dense nuclear Fos staining was induced throughout the ventral arcuate nucleus of rats injected intracerebrove ntricularly with low doses of GHRP-6 but not in rats injected with the endogenous GH-releasing hormone GHRH or in vehicle-treated controls. The non-peptidyl GH secretagogues L-692,585 and Lr 692,429 also induce d Fos expression in the arcuate nucleus, and the pattern of distributi on was similar to that described for GHRP-6. No increase in Fos expres sion was observed in rats given a systemic injection of a high dose of GHRH. In pentobarbitone-anaesthetized male rats, the effects of intra venous injection of GHRP-6 on the electrical activity of arcuate neuro nes was predominantly excitatory for putative neuroendocrine cells and inhibitory for the remaining unidentified cells. These results sugges t that (1) GHRP-6 and nonpeptidyl GH secretagogues have a central site of action involving the activation nucleus of a subpopulation of arcu ate neurones and (2) this action is not mimicked by the central or per ipheral effects of GHRH.