Investigation of the feeding effects of melanin concentrating hormone on food intake - action independent of galanin and the melancortin receptors

Melanin concentrating hormone (MCH) is recognised as a hypothalamic appetite stimulant. The mechanism of action of MCH is undetermined largely due to lack of identification of hypothalamic MCH receptors. We designed in vivo and in vitro studies to further characterise the feeding effects of MCH in the rat. MCH was injected directly into the paraventricular nucleus (PVN) at the beginning of the light phase. PVN MCH (0.5 mu g) produced an increase in 2 h food intake of 272 +/- 60% vs. saline control (0.7 +/- 0.2 g), p < 0.05. The time course of the effect of intracerebroventricular (i.c.v.) administration of 5 mu g MCH on food intake was investigated. An increase in feeding was observed within 15 min from the time of injection and was not sustained beyond half an hour following administration. To investigate a possible interaction with galanin, 5 mu g of MCH was injected i.c.v. with or without 10 mu g of galanin. The two peptides together increased 1 h feeding above that of either peptide alone, 768 +/- 62% (compared with the saline group, 0.47 +/- 0.2 g), p < 0.05 vs. 585 +/- 36%, galanin alone and 317 +/- 72%, MCH alone. Finally, to investigate if MCH bound to the brain melanocortin receptors, receptor autoradiography was performed on rat brain sections with the stable analogue of alpha MSH, [I-125] Nle(4), D-Phe(7)-alpha MSH and unlabeled MCH. MCH did not compete with [I-125] Nle4, D-Phe(7)-alpha MSH binding. Results demonstrate that MCH stimulates feeding via the PVN, has a short onset and duration of action and activates feeding by mechanisms independent to galanin and the melanocortin receptors. (C) 1999 Elsevier Science B.V. All rights reserved.