Inhibitory effects of partial D2 dopamine receptor agonists on the d-amphetamine discriminative cue

The ability of partial dopamine (DA) receptor agonists with low relative efficacy to inhibit the d-amphetamine discriminative cue has been determined in rats trained to discriminate 0.5mg/kg d-amphetamine from saline. The classical neuroleptic haloperidol and selective D1 antagonist SCH 23390 potently blocked the cueing properties of d-amphetamine. A complete blockade of d-amphetamine discrimination was also observed with the partial DA agonist terguride. In contrast, preclamol [(-)-3-PPP] and SDZ 208-911 produced only a partial inhibition which was characterized by an asymptotic drug effect across a wide dose range. Clear variations in the sensitivity of individual rats to the inhibitory effects of preclamol on the d-amphetamine cue were observed. Some rats were sensitive to even low doses of preclamol, while others were minimally affected across the dose range. Variations in individual response were also observed with SDZ 208-911 and terguride, but not with haloperidol or SCH 23390. The present findings are discussed in relation to the partial agonist profile of preclamol, SDZ 208-911 and terguride and to possible underlying differences in DA receptor sensitivity between individual rats.