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

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.