Some of the effects of the selective sigma ligand (+)pentazocine are mediated via a naloxone-sensitive receptor

Recently, in an attempt to isolate the nonopioid a receptor, Su and colleagues purified a protein from rat liver and brain which appeared to resemble the original a opioid receptor as proposed by Martin in 1976, and for which the nonopiate a, ligand (+)pentazocine presents a high affinity. Previous in vivo electrophysiological studies from our laboratory have demonstrated that several selective a, ligands potentiate the neuronal response to NMDA. The goal of the present series of experiments was to assess the effects of some selective a, ligands on the potentiation of the NMDA response and to determine if this potentiation was mediated by the naloxone-sensitive a receptor. Extracellular unitary recordings from pyramidal neurons of the CA, region of the rat dorsal hippocampus were obtained. The a, ligands ED 737, L 687-384, and JO-1784 (igmesine), administered intravenously at low doses, potentiated the NMDA response but the opiate antagonist naloxone failed to reverse this potentiation. However, the potentiation of the NMDA response induced by the a, ligand (+)pentazocine was suppressed by naloxone but not by the mu antagonist cyprodime hydrobomide, the kappa antagonist DIPPA nor by the delta antagonist naltrindole. (+/-) Cyclazocine, which presents a high affinity for the above-mentioned sigma -opiate receptor acted as an antagonist by suppressing the potentiation of the NMDA response induced by both JO-1784 and (+)pentazocine. These results suggest that the effects induced by some a, ligands may, in fact, be sensitive to naloxone while others may not. The original classification of a receptors as opiates might have been partly accurate. Synapse 39:323-331, 2001. (C) 2001 Wiley-Liss, Inc.