Kappa opioid receptor inhibition of glutamatergic transmission in the nucleus accumbens shell.
Microinjection of kappa-opioid receptor agonists into the nucleus accumbens produces conditioned place aversion. While attention has focused primarily on the inhibition of dopamine release by kappa-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 kappa-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 kappa-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 kappa-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 kappa-receptor-mediated aversion observed in intact animals.
Department of Neurology, The W. M. Keck Center for Integrative Neuroscience and The Wheeler Center for the Neurobiology of Addiction, University of California, San Francisco, California 94143, USA. goh@phy.ucsf.edu
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D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D044482:Benzeneacetamides; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000819:agonists; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D044482:Benzeneacetamides; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D011759:Pyrrolidines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D018698:Glutamic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; C045444:U 69593