The Journal of Neurophysiology Vol. 85 No. 3 March 2001, pp. 1153-1158
Copyright ©2001 by the American Physiological Society

Kappa Opioid Receptor Inhibition of Glutamatergic Transmission in the Nucleus Accumbens Shell

Departments of Neurology and Physiology, The W. M. Keck Center for Integrative Neuroscience and The Wheeler Center for the Neurobiology of Addiction, University of California, San Francisco, California 94143

Hjelmstad, Gregory O. and Howard L. Fields. Kappa Opioid Receptor Inhibition of Glutamatergic Transmission in the Nucleus Accumbens Shell. J. Neurophysiol. 85: 1153-1158, 2001. Microinjection of -opioid receptor agonists into the nucleus accumbens produces conditioned place aversion. While attention has focused primarily on the inhibition of dopamine release by -receptor agonists as the synaptic mechanism underlying this effect, recent anatomical studies have raised the possibility that regulation of noncatecholaminergic transmission also contribute. We have investigated the effects of -receptor activation on fast excitatory synaptic transmission in an in vitro slice preparation using whole cell voltage-clamp or extracellular field recordings in the shell region of the nucleus accumbens. The -receptor agonist U69593 produces a pronounced, dose-dependent inhibition of glutamatergic excitatory postsynaptic currents (EPSCs) that can be reversed by 100 nM nor-BNI. Furthermore, U69593 causes an increase in the paired-pulse ratio as well as a decrease in the frequency of spontaneous miniature events, suggesting a presynaptic site of action. Despite anatomical evidence for -receptor localization on dendritic spines of nucleus accumbens neurons, no electrophysiological evidence of a postsynaptic effect was found. This presynaptic inhibition of excitatory synaptic transmission in the nucleus accumbens shell provides a novel mechanism that may contribute to the -receptor-mediated aversion observed in intact animals.