J Neurophysiol (May 1, 2003). 10.1152/jn.01115.2002
Submitted on Submitted 11 December 2002; accepted in final form 27 January 2003

Kappa Opioid Receptor Activation in the Nucleus Accumbens Inhibits Glutamate and GABA Release Through Different Mechanisms

Department of Neurology, Ernest Gallo Clinic and Research Center, 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 Activation in the Nucleus Accumbens Inhibits Glutamate and GABA Release Through Different Mechanisms. J. Neurophysiol. 89: 2389-2395, 2003. Through their actions in the nucleus accumbens (NAc), kappa opioid (KOP) receptors and their endogenous ligand, dynorphin, modify behaviors associated with the administration of drugs of abuse and are regulated by exposure to such drugs. Despite their demonstrated behavioral significance, the synaptic actions of KOP receptor ligands in the NAc are not clearly understood. Using whole-cell voltage-clamp recordings of NAc medium spiny neurons, we have found that, in addition to suppressing glutamate release, the KOP receptor agonist U69593 also inhibits GABA release. Interestingly, the mechanism of inhibition of the release of glutamate differs from that controlling GABA. U69593 reduces the frequency of Ca²⁺-independent miniature excitatory postsynaptic currents, but not miniature inhibitory postsynaptic currents. Furthermore, while the U69593 inhibition of GABAergic transmission is blocked by the N-type Ca²⁺ channel blocker -CgTx, the inhibition of excitatory glutamatergic transmission by U69593 is unaffected by N-type Ca²⁺ channel blockade. These results indicate that KOP receptor activation inhibits GABA release by reducing Ca²⁺ influx, but inhibits glutamate release at a step downstream of Ca²⁺ entry.