D(1) AND D(2) DOPAMINE RECEPTOR-MEDIATED MECHANISMS AND BEHAVIORAL SUPERSENSITIVITY

The contribution of D1 and D2 dopamine (DA) receptor mechanisms to the behavioral supersensitivity and receptor upregulation induced by chro nic DA antagonist administration were compared. Rats received either t he selective D1 DA receptor antagonist SCH23390, the selective D2 DA r eceptor antagonist raclopride, their combination, or haloperidol, a pr edominantly D2 antagonist, for 21 days. Equivalent cataleptogenic dose s of all drugs and drug combinations were employed. Tolerance to the c ataleptic response was observed only in the haloperidol-treated group. Apomorphine-induced stereotypies were significantly enhanced in SCH23 390-, raclopride-, and haloperidol-treated rats. In contrast, coadmini stration of both SCH23390 and raclopride had no effect on apomorphine- induced stereotypy. These findings suggest that neuroleptics blocking in equal proportion D1 and D2 receptor sites might be less likely to i nduce tardive dyskinesia and drug tolerance than those acting selectiv ely on one or the other of these receptor subtypes.