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Volume 16, Number 13, Issue of July 1, 1996 pp. 4162-4173
Copyright ©1996 Society for Neuroscience

Ultrastructural Immunocytochemical Localization of µ-Opioid Receptors in Rat Nucleus Accumbens: Extrasynaptic Plasmalemmal Distribution and Association with Leu⁵-Enkephalin

Received Oct. 11, 1995; revised April 18, 1996; accepted April 24, 1996.

Adena L. Svingos¹, Akiyoshi Moriwaki², Jia Bei Wang², George R. Uhl², and Virginia M. Pickel¹

¹ Division of Neurobiology, Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021, and ² Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, and Departments of Neurology and Neuroscience, The Johns Hopkins University, Baltimore, Maryland 21224

µ-Opioid receptors and their endogenous ligands, including Leu⁵-enkephalin (LE), are distributed abundantly in the nucleus accumbens (NAC), a region implicated in mechanisms of opiate reinforcement. We used immunoperoxidase and/or immunogold-silver methods to define ultrastructural sites for functions ascribed to µ-opioid receptors and potential sites for activation by LE in the NAC. An antipeptide antibody raised against an 18 amino acid sequence of the cloned µ-opioid receptor (MOR) C terminus showed that MOR-like immunoreactivity (MOR-LI) was localized predominantly to extrasynaptic sites along neuronal plasma membranes. The majority of neuronal profiles containing MOR-LI were dendrites and dendritic spines. The dendritic plasma membranes immunolabeled for MOR were near sites of synaptic input from LE-labeled terminals and other unlabeled terminals forming either inhibitory or excitatory type synapses. Unmyelinated axons and axon terminals were also intensely but less frequently immunoreactive for MOR. Observed sites for potential axonal associations with LE included coexistence of MOR and LE within the same terminal, as well as close appositions between differentially labeled axons. Astrocytic processes rarely contained detectable MOR-LI, but also were sometimes observed in apposition to LE-labeled terminals. We conclude that in the rat NAC, MOR is localized prominently to extrasynaptic neuronal and more rarely to glial plasma membranes that are readily accessible to released LE and possibly other opioid peptides and opiate drugs. The close affiliation of MOR with spines receiving excitatory synapses and dendrites receiving inhibitory synapses provides the first direct morphological evidence that MOR selectively modulates postsynaptic responses to cortical and other afferents.

Key words: µ-opioid receptor; reinforcement; striatum; enkephalin; morphine; opiates

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