Tonic inhibition of food intake during inactive phase is reversed by the injection of the melanocortin receptor antagonist into the paraventricular nucleus of the hypothalamus and central amygdala of the rat

Melanocortins inhibit food intake and melanocortin 4 receptor (MC4R) antago nists stimulate feeding behaviour. These effects may occur due to stimulati on or blockade of MC4 receptors in the hypothalamus. To test the validity o f this hypothesis, a cyclic peptide, the MC4R selective antagonist HS014 (2 0, 100 and 500 pmol), or vehicle, was injected unilaterally into the parave ntricular nucleus of the hypothalamus (PVN). As MC receptors are expressed also in extrahypothalamic sites involved in the regulation of feeding behav iour, HS014 was injected bilaterally into the vicinity of the central nucle us of the amygdala (CA) and the nucleus accumbens region (Acc). All doses o f HS014 induced a dose-dependent increase in food intake when injected into the PVN. Intra-amygdalar injections of HS014 (50 and 250 pmol/side) also s timulated food intake, whereas a 10-pmol dose was inactive. Local microinje ctions of HS014 into the Acc failed to stimulate feeding. These data sugges t that endogenous melanocortin receptor agonists exert a tonic inhibitory i nfluence on food consumption by stimulating MC4 receptors in the hypothalam us and amygdala. (C) 2000 Elsevier Science B.V. All rights reserved.