Effects of the opioid antagonist naltrexone on feeding induced by DAMGO in the central nucleus of the amygdala and in the paraventricular nucleus in the rat

The paraventricular nucleus of the hypothalamus (PVN) and the central nucleus of the amygdala (CNA) are two forebrain structures which are important in regulation of ingestive behavior. DAMGO is one of the most reliable and potent mu-selective opioid ligands that increases feeding in both of these brain nuclei. Administration of naloxone, an opioid antagonist, into the CNA prior to DAMGO blocks DAMGO-induced increases in food intake. The effect of this drug combination on food intake has not been evaluated in the PVN. However, intra-PVN injection of naloxone decreases deprivation and NPY-induced feeding. It has been suggested that CNA may modulate activity of midbrain and caudal brainstem centers via the hypothalamus. Based on these data, we evaluated whether an opioid-opioid interaction is present between the CNA and PVN which might affect feeding behavior. To test this, rats were doubly cannulated with 1 cannula placed in the PVN and 1 cannula in the CNA, allowing for co-administration of the opioid agonist into the PVN and the opioid antagonist into the CNA, and vice versa. CNA DAMGO increased feeding more than two-fold as compared to the vehicle-injected rats. When doses of 10, 12.5 and 25 mu g Of naltrexone (NTX) were injected into the PVN, CNA DAMGO no longer increased food intake above control levels. In the reverse situation, PVN DAMGO also increased food intake above control levels. However, when NTX was administrated unilaterally into the CNA at a relatively high dose (25 mu g) or bilaterally (12.5 mu g), PVN DAMGO-induced feeding was not altered. This suggests chat an opioid-opioid signaling pathway exists from the CNA to the PVN which influences feeding via mu opioid receptors, whereas such a pathway from the PVN to the CNA does not seem to exist. (C) 1998 Elsevier Science B.V.