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

Cholinergic interneurons in the nucleus accumbens shell (AcbSh) are implica ted in the reinforcing behaviors that develop in response to opiates active at mu -opioid receptors (MOR). We examined the electron microscopic immuno cytochemical localization of the vesicular acetylcholine transporter (VAChT ) and MOR to determine the functional sites for storage and release of acet ylcholine (ACh), and potential interactions involving MOR in this region of rat brain. VAChT was primarily localized to membranes of small synaptic ve sicles in axon terminals. Less than 10% of the VAChT-labeled terminals were MOR-immunoreactive. In contrast, 35% of the cholinergic terminals formed s ymmetric or punctate synapses with dendrites showing an extrasynaptic plasm alemmal distribution of MOR. Membranes of tubulovesicles in other selective dendrites were also VAChT-labeled, and almost half of these dendrites disp layed plasmalemmal MOR immunoreactivity. The VAChT-labeled dendritic tubulo vesicles often apposed unlabeled axon terminals that formed symmetric synap ses. Our results indicate that in the AcbSh MOR agonists can modulate the r elease of ACh from vesicular storage sites in axon terminals as well as in dendrites where the released ACh may serve an autoregulatory function invol ving inhibitory afferents. These results also suggest, however, that many o f the dendrites of spiny projection neurons in the AcbSh are dually influen ced by ACh and opiates active at MOR, thus providing a cellular substrate f or ACh in the reinforcement of opiates. Synapse 40:184-192, 2001. (C) 2001 Wiley-Liss, Inc.