CGS 10746B is able to attenuate the effects of amphetamine: Further evidence for dopaminergic mediation

Abstract

Previous results indicate that agents which either decrease synthesis or block postsynaptic dopamine receptors will attenuate the discriminative stimulus produced by d-amphetamine. CGS 10746B has been reported to decrease dopamine release without changing its metabolism or occupying its receptors. In the present study, rats successfully trained to discriminate intraperitoneally administered (0.8 mg/kg) d-amphetamine in a two-lever, food-motivated operant task were observed to be unable to discriminate amphetamine when pretreated with 30 mg/kg CGS 10746B. This antagonism was shown to be dose-responsive and constitutes a third mechanism, i.e., dopamine release inhibition, that evidences the dopaminergic mediation of amphetamine in the discriminative paradigm. When both cathinone (0.8 mg/kg) and cocaine (10.0 mg/kg) were administered to the amphetamine-trained rats they each were recognized as amphetamine and are, thus, considered to generalize to the amphetamine discriminative stimulus. Coadministration of CGS 10746B and cathinone totally antagonized this generalization, whereas pretreatment with CGS 10746B prior to cocaine significantly reduced cocaine's effects. These results implicate dopamine mechanisms in the discriminative stimulus properties of the psychostimulants amphetamine, cathinone and cocaine.