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Koyama, S and Akaike, N (2008) Activation of mu-opioid receptor selectively potentiates NMDA-induced outward currents in rat locus coeruleus neurons. Neurosci. Res. 60:22-8


We investigated the opioid modulation of N-methyl-d-aspartic acid (NMDA) receptor-mediated response in dissociated LC neurons using nystatin-perforated patch recording. In Mg(2+)-free extracellular solution, NMDA induced an inward current (I(NMDA-IN)) and a subsequent outward current (I(NMDA-OUT)) at a holding potential of -40 mV. A selective mu-opioid receptor agonist, d-Ala(2),N-MePhe(4),Gly(5)-ol-enkephalin (DAMGO), potentiated I(NMDA-OUT) in a concentration-dependent manner with the half-maximal effective concentration of 0.7 microM, while DAMGO (0.1-10 microM) did not affect I(NMDA-IN). Under the condition of I(NMDA-OUT) blockade by the use of Cs-based pipette solution or by buffering intracellular Ca(2+) with a high concentration of EGTA and zero Ca(2+), DAMGO did not change I(NMDA-IN). The DAMGO potentiation of I(NMDA-OUT) was prevented by naloxone, an opioid receptor antagonist. In addition, the DAMGO potentiation of I(NMDA-OUT) was prevented by treatment with staurosporine, a broad spectrum protein kinase inhibitor. In conclusion, mu-opioid receptor activation selectively potentiated I(NMDA-OUT) via intracellular signal pathway without affecting I(NMDA-IN) in LC neurons. We suggest the inhibitory opioid effect through NMDA receptor-mediated response in LC neurons.


PubMed Online version:10.1016/j.neures.2007.09.003


Action Potentials/drug effects; Action Potentials/physiology; Analgesics, Opioid/pharmacology; Animals; Dose-Response Relationship, Drug; Drug Synergism; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/pharmacology; Enzyme Inhibitors/pharmacology; Excitatory Amino Acid Agonists/pharmacology; Glutamic Acid/metabolism; Locus Coeruleus/drug effects; Locus Coeruleus/metabolism; N-Methylaspartate/pharmacology; Narcotic Antagonists/pharmacology; Neural Inhibition/drug effects; Neural Inhibition/physiology; Organ Culture Techniques; Patch-Clamp Techniques; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate/drug effects; Receptors, N-Methyl-D-Aspartate/metabolism; Receptors, Opioid, mu/agonists; Receptors, Opioid, mu/metabolism; Synaptic Transmission/drug effects; Synaptic Transmission/physiology