The central nucleus of the amygdala (CeA) and the nucleus of the accumbens shell (NAc) have been shown to be involved in opioid-mediated feeding behavior. The present study examined whether mu-opioid signalling between the CeA and NAc affected feeding. Male Sprague-Dawley rats were fitted with one cannula placed in the CeA and two cannulae placed in the NAc, which allowed for coadministration of the mu-opioid receptor agonist [D-Ala(2), NMe-Phe(4), Gly-ol(5)]-enkephalin (DAMGO) in one site and the opioid antagonist naltrexone (NTX) in the other site. Single injection of DAMGO (2.4 nmol) into the CeA and bilateral injections of DAMGO (2.4 nmol) into the NAc stimulated feeding (P<0.05). The DAMGO-induced increase of food intake following injection into the CeA was decreased by bilateral injection of NTX (13.2 and 26.5 nmol) into the NAc at 2- and 4-h postinjections (P<0.05). In the reverse situation, the DAMGO-induced increase of food intake following injection into the NAc was decreased by injection of NTX (13.2 and 26.5 nmol) into the CeA at 1-, 2-, and 4-h postinjections (P<0.05). These results suggest that a bi-directional mu-opioid-opioid signalling pathway exists between the CeA and the NAc, which influences feeding.