A putative sigma1 receptor antagonist NE-100 attenuates the discriminative stimulus effects of ketamine in rats.

Ketamine, one of the dissociative anaesthetic agents, has been shown to produce psychotomimetic effects. It has been well documented that activation of sigma receptors is responsible for the pathogenesis of some psychiatric disorders. In the present study, the effects of NE-100, a putative sigma(1) receptor antagonist, was investigated in rats trained to discriminate between ketamine (5 mg/kg, i.p.) from saline under a fixed-ratio 10 food-reinforced procedure. Here we report for the first time that NE-100 (1 mg/kg) produced a shift to the right in the dose-response curve for ketamine's discriminative stimulus effects. These results suggest that the sigma(1) receptor is, at least in part, involved in the discriminative stimulus effects of ketamine.