The present study investigated the cellular localization of mu, delta and kappa opioid receptors in the rat nucleus accumbens in relation to dopaminergic neurons. Dopaminergic terminals were destroyed by intra-accumbens injections of the neurotoxin 6-hydroxydopamine (6-OHDA). Fourteen days after dopaminergic denervation, receptor binding assays and quantitative in vitro autoradiography with highly selective radioligands demonstrated that the density of mu opioid receptors in the nucleus accumbens was decreased by 30 +/- 6%. There was no change in delta or kappa receptors in the accumbens, a finding which indicates that the loss of mu opioid receptors was specific. A time course study demonstrated that the loss of mu receptors lagged behind the depletion of dopamine by about 5 days. Destruction of intrinsic neuronal cell bodies and dendrites by injection of ibotenic acid into the accumbens resulted in a loss of 36 +/- 3% of mu opioid receptors. Co-injection of 6-OHDA and ibotenic acid decreased mu receptors by 41 +/- 4%, only slightly more than the loss caused by ibotenic acid alone. These results suggest that only a small number of mu opioid receptors in the nucleus accumbens are located on dopaminergic terminals and are consistent with the possibility that the loss of opioid receptors following denervation of dopaminergic fibers in the accumbens is the result of transsynaptic degeneration.