Sigma-1 receptor function is critical for both the discriminative stimulus and aversive effects of the kappa-opioid receptor agonist U-50488H.

Tomohisa Mori, Kazumi Yoshizawa, Mutsuko Nomura, Kana Isotani, Kazuhiro Torigoe, Yoshi Tsukiyama, Minoru Narita, Tsutomu Suzuki

Index: Addict. Biol. 17(4) , 717-24, (2012)

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Abstract

The present study was undertaken to identify possible similarities between the effects of kappa-opioid receptor agonist, N-methyl-D-aspartate-receptor antagonist, and sigma receptor agonist on the discriminative stimulus effects of U-50488H, and the possible involvement of sigma receptors in the discriminative stimulus and aversive effects of U-50488H. The kappa-opioid receptor agonist U-50488H produced significant place aversion as measured by the conditioned place preference procedure, and this effect was completely abolished by treatment with the putative sigma-1 receptor antagonist NE-100. In addition, phencyclidine (+)-SKF-10047 and (+)-pentazocine, which are sigma receptor agonists, generalized to the discriminative stimulus effects of U-50488H in rats that had been trained to discriminate between U-50488H (3.0 mg/kg) and saline. Furthermore, NE-100 significantly attenuated the discriminative stimulus effects of U-50488H and the U-50488H-like discriminative stimulus effects of phencyclidine. These results suggest that the sigma-1 receptor is responsible for both the discriminative stimulus effects and aversive effects of U-50488H.© 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.