Plasmalemmal mu-opioid receptor distribution mainly in nondopaminergic neurons in the rat ventral tegmental area

Opiate-evoked reward and motivated behaviors reflect, in part, the enhanced release of dopamine produced by activation of the mu -opioid receptor (mu OR) in the ventral tegmental area (VTA). We examined the functional sites f or mu OR activation and potential interactions with dopaminergic neurons wi thin the rat VTA by using electron microscopy for the immunocytochemical lo calization of antipeptide antisera raised against mu OR and tyrosine hydrox ylase (TH), the synthesizing enzyme for catecholamines. The cellular and su bcellular distribution of mu OR was remarkably similar in the two major VTA subdivisions, the paranigral (VTApn) and parabrachial (VTApb) nuclei. In e ach region, somatodendritic profiles comprised over 50% of the labeled stru ctures. mu OR immunolabeling was often seen at extrasynaptic/perisynaptic s ites on dendritic plasma membranes, and 10% of these dendrites contained TH . mu OR-immunoreactivity was also localized to plasma membranes of axon ter minals and small unmyelinated axons, none of which contained TH. The mu OR- immunoreactive axon terminals formed either symmetric or asymmetric synapse s that are typically associated with inhibitory and excitatory amino acid t ransmitters. Their targets included unlabeled (30%), mu OR-labeled (25%), a nd TH-labeled (45%) dendrites. Our results suggest that mu OR agonists in t he VTA affect dopaminergic transmission mainly indirectly through changes i n the postsynaptic responsivity and/or presynaptic release from neurons con taining other neurotransmitters. They also indicate, however, that mu OR ag onists directly affect a small population of dopaminergic neurons expressin g mu OR on their dendrites in VTA and/or terminals in target regions. (C) 2 001 Wiley-Liss, Inc.