Discriminative stimulus properties of a sigma receptor agonist in the rat: role of monoamine systems.

The role of the dopaminergic, noradrenergic and serotonergic systems in the production of the discriminative stimulus (DS) properties of the sigma receptor agonist (+)-N-allylnormetazocine [(+)-NANM/(+)-SKF 10,047] was measured in rats. The partial generalization of the noradrenergic agonist clonidine with (+)-NANM and partial antagonism of (+)-NANM by yohimbine suggest that the noradrenergic system may play a role in (+)-NANM DS. Activation of the dopaminergic system by apomorphine did not produce (+)-NANM DS however, haloperidol, which binds to the sigma receptor with high affinity, antagonized (+)-NANM DS. These data suggest that the haloperidol antagonism of (+)-NANM DS is a function of antagonism at the sigma receptor rather than antagonism at the dopamine receptor. Since yohimbine does not bind to the sigma receptor, yohimbine antagonizes (+)-NANM by a mechanism different from that of haloperidol. There was no evidence to suggest serotonergic mediation of (+)-NANM DS.