Kappa opioid receptor inhibition of glutamatergic transmission in the nucleus accumbens shell

Microinjection of kappa -opioid receptor agonists into the nucleus accumben s produces conditioned place aversion. While attention has focused primaril y on the inhibition of dopamine release by kappa -receptor agonists as the synaptic mechanism underlying this effect, recent anatomical studies have r aised the possibility that regulation of noncatecholaminergic transmission also contribute. We have investigated the effects of kappa -receptor activa tion on fast excitatory synaptic transmission in an in vitro slice preparat ion using whole cell voltage-clamp or extracellular field recordings in the shell region of the nucleus accumbens. The kappa -receptor agonist U69593 produces a pronounced, dose-dependent inhibition of glutamatergic excitator y postsynaptic currents (EPSCs) that can be reversed by 100 nM nor-BNI. Fur thermore, U69593 causes an increase in the paired-pulse ratio as well as a decrease in the frequency of spontaneous miniature events, suggesting a pre synaptic site of action. Despite anatomical evidence for kappa -receptor lo calization on dendritic spines of nucleus accumbens neurons, no electrophys iological evidence of a postsynaptic effect was found. This presynaptic inh ibition of excitatory synaptic transmission in the nucleus accumbens shell provides a novel mechanism that may contribute to the kappa -receptor-media ted aversion observed in intact animals.