Vesicular acetylcholine transporter in the rat nucleus accumbens shell: subcellular distribution and association with mu-opioid receptors.

Abstract

Cholinergic interneurons in the nucleus accumbens shell (AcbSh) are implicated in the reinforcing behaviors that develop in response to opiates active at mu-opioid receptors (MOR). We examined the electron microscopic immunocytochemical localization of the vesicular acetylcholine transporter (VAChT) and MOR to determine the functional sites for storage and release of acetylcholine (ACh), and potential interactions involving MOR in this region of rat brain. VAChT was primarily localized to membranes of small synaptic vesicles in axon terminals. Less than 10% of the VAChT-labeled terminals were MOR-immunoreactive. In contrast, 35% of the cholinergic terminals formed symmetric or punctate synapses with dendrites showing an extrasynaptic plasmalemmal distribution of MOR. Membranes of tubulovesicles in other selective dendrites were also VAChT-labeled, and almost half of these dendrites displayed plasmalemmal MOR immunoreactivity. The VAChT-labeled dendritic tubulovesicles often apposed unlabeled axon terminals that formed symmetric synapses. Our results indicate that in the AcbSh MOR agonists can modulate the release of ACh from vesicular storage sites in axon terminals as well as in dendrites where the released ACh may serve an autoregulatory function involving inhibitory afferents. These results also suggest, however, that many of the dendrites of spiny projection neurons in the AcbSh are dually influenced by ACh and opiates active at MOR, thus providing a cellular substrate for ACh in the reinforcement of opiates.