Quipazine-induced stimulus control in the rat

Abstract

The present investigation tested the hypothesis that quizapine, a drug thought to act directly or indirectly as an agonist at serotonergic (5-HT) receptors, mimics the stimulus properties of indoleamine and phenethylamine hallucinogens. In a group trained with mescaline (10 mg/kg) and saline in a singlelever response rate task, quipazine yielded intermediate results (58% mescaline-appropriate at 1 mg/kg), i.e., responding was fully appropriate for neither training condition. A second group was then trained with quipazine (3 mg/kg) and saline in a two-lever response choice task. Stimulus control was readily established with a mean of 22 sessions to achieve criterion performance (five consecutive sessions with at least 80% correct responses). When quipazine-trained rats were tested with LSD; responding was intermediate in nature (68% quipazine-appropriate) at a dose of 100 μg/kg but complete substitution was observed at 150 μg/kg (97% quipazine-appropriate). Similarly, subjects trained with LSD and saline in the two lever task and tested with quipazine responded in a fashion indistinguishable from the LSD training condition. The stimulus properties of quipazine alone and in cross tests in mescaline or LSD-trained subjects were blocked by the serotonergic antagonist, BC-105. Butaclamol, a dopaminergic antagonist, and the α-adrenergic antagonist, phentolamine, were without effect upon quipazine. The present data suggest that quipazine produces its stimulus effects by a serotonergic mechanism and that these effects are quite similar to those of LSD and mescaline.