Kappa opioid receptor activation in the nucleus accumbens inhibits glutamate and GABA release through different mechanisms.
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 also inhibits GABA release. Interestingly, the mechanism of inhibition of the release of glutamate differs from that controlling GABA. reduces the frequency of Ca(2+)-independent miniature excitatory postsynaptic currents, but not miniature inhibitory postsynaptic currents. Furthermore, while the inhibition of GABAergic transmission is blocked by the N-type Ca(2+) channel blocker omega-CgTx, the inhibition of excitatory glutamatergic transmission by is unaffected by N-type Ca(2+) channel blockade. These results indicate that KOP receptor activation inhibits GABA release by reducing Ca(2+) influx, but inhibits glutamate release at a step downstream of Ca(2+) entry.
Department of Neurology, Ernest Gallo Clinic and Research Center, Emeryville, California 94143, USA. goh@phy.ucsf.edu
Gregory O
GO
Hjelmstad
Howard L
HL
Fields
D000700:Analgesics / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D044482:Benzeneacetamides; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000187:drug effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005971:Glutamates / Q000378:metabolism*; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000502:physiology
D000700:Analgesics; D000701:Analgesics, Opioid; D044482:Benzeneacetamides; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D005971:Glutamates; D018377:Neurotransmitter Agents; D015221:Potassium Channels; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D002104:Cadmium; D005680:gamma-Aminobutyric Acid; C045444:U 69593; D002118:Calcium