Reward is an important factor motivating food intake in satiated animals. Two sites involved in the reward response are the ventral tegmental area (VTA) and the nucleus accumbens shell region (sNAcc), between which communication is partially regulated by opioids and dopamine (DA). Previous studies have shown that the mu-opioid agonist Tyr-D-Ala-Gly-MePhe-Gly(ol)-enkephalin (DAMGO) dose-dependently enhances food intake in satiated animals when injected into either the VTA or the sNAcc. The enhanced intake elicited by DAMGO injected into the sNAcc was dose-dependently blocked by injection of naltrexone (NTX) bilaterally into the VTA, indicating an opioid-dependent signaling pathway from the sNAcc to the VTA in mediation of food intake. In the present study, we cannulated animals bilaterally in both the VTA and the sNAcc to further study the nature of opioid- and DA-dependent communication between the sites. Food intake elicited by DAMGO (2 or 5 nmol) injected unilaterally into the VTA was dose-dependently diminished by bilateral injection of NTX (2.5, 5, and 25 g/side) or the D1 antagonist SCH 23390 (3, 1, 0.3, 0.15, 0.05, and 0.015 nmol/side) into the sNAcc. When DAMGO (5 nmol) was injected into the sNAcc, the resulting food intake was decreased by doses of SCH 23390 ranging from 0.05 to 100 nmol/side injected bilaterally into the VTA, but not by equimolar doses of Raclopride, a D2 antagonist. These results, combined with previous findings, suggest a signaling pathway between the VTA and the sNAcc in which opioids and DA facilitate feeding in an interdependent manner.