Plasmalemmal μ-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 for mu OR activation and potential interactions with dopaminergic neurons within the rat VTA by using electron microscopy for the immunocytochemical localization of antipeptide antisera raised against mu OR and tyrosine hydroxylase (TH), the synthesizing enzyme for catecholamines. The cellular and subcellular distribution of mu OR was remarkably similar in the two major VTA subdivisions, the paranigral (VTApn) and parabrachial (VTApb) nuclei. In each region, somatodendritic profiles comprised over 50% of the labeled structures. mu OR immunolabeling was often seen at extrasynaptic/perisynaptic sites on dendritic plasma membranes, and 10% of these dendrites contained TH. mu OR-immunoreactivity was also localized to plasma membranes of axon terminals and small unmyelinated axons, none of which contained TH. The mu OR-immunoreactive axon terminals formed either symmetric or asymmetric synapses that are typically associated with inhibitory and excitatory amino acid transmitters. Their targets included unlabeled (30%), mu OR-labeled (25%), and TH-labeled (45%) dendrites. Our results suggest that mu OR agonists in the VTA affect dopaminergic transmission mainly indirectly through changes in the postsynaptic responsivity and/or presynaptic release from neurons containing other neurotransmitters. They also indicate, however, that mu OR agonists directly affect a small population of dopaminergic neurons expressing mu OR on their dendrites in VTA and/or terminals in target regions. (C) 2001 Wiley-Liss, Inc.