Discriminative stimulus effects of the alpha 2-adrenoceptor antagonist idazoxan

Rats were trained to discriminate a dose of the alpha 2-adrenoceptor antagonist idazoxan (10 mg/kg IP) from saline. The discriminative stimulus produced by idazoxan was dose related and generalised to yohimbine. However, generalisation did not occur with a variety of compounds from other pharmacological categories including the alpha 1-adrenoceptor agonist cirazoline, the alpha 1-adrenoceptor antagonist prazosin, and the alpha 2-adrenoceptor agonist clonidine. The idazoxan stimulus was not antagonised by either prazosin or clonidine, although it was clear that idazoxan antagonised the reductions in response rate produced by clonidine. Dose-related responding on the idazoxan-associated lever was produced by the anxiolytics buspirone and ipsapirone and by their metabolite MJ 13653 (1-PP), which has previously been shown to be an alpha 2-adrenoceptor antagonist. In general, however, high levels of generalisation occurred with these three compounds only at doses which substantially reduced response rates. These results demonstrate that idazoxan can give rise to a discriminative stimulus which is probably mediated through antagonism at alpha 2-adrenoceptors although the failure of clonidine to block the idazoxan stimulus is difficult to explain.