Discriminative stimulus properties of antipsychotics

Drug discrimination methodology has been used in a number of ways to analyz e the actions of novel and putative novel antipsychotics in vivo. Recent st udies suggest (a) in contrast to earlier theorizing, antagonism of the low- dose d-amphetamine stimulus in rats may not be an effective screen for nove l antipsychotics; (b) dopamine D-2-like agonists and antagonists, some of w hich are putative antipsychotics, can be studied in vivo as discriminative cues, although there is a pressing need for more selective drugs that diffe rentiate the various members of the D-2 family; (c) antagonism of the cue i nduced by the noncompetitive NMDA antagonist MK-801, which has been propose d as a possible screen for clozapine-like compounds, may be an unreliable a ssay; and (d) the clozapine stimulus is probably a compound cue (a drug "mi xture"), which can be used to screen for novel clozapine-like antipsychotic s, although the precise receptor mechanisms involved in mediating the cloza pine stimulus, and its direct relevance to the antipsychotic action of cloz apine remains to be proven conclusively. (C) 1999 Elsevier Science Inc.