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.
Hjelmstad
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GO
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