Comparison of the stimulus properties of a pre- vs a putative postsynaptic dose of quinpirole

Presynaptic D-2-like receptors appear to mediate the stimulus properties of a low dose (0.05 mg/kg) of the D-2-like agonist quinpirole (QUIN), because treatments decreasing dopamine (DA) release or blocking postsynaptic DA receptor activation produce QUIN-appropriate responding in a drug discrimination context, whereas treatments activating postsynaptic DA receptors evoke saline responding (28). This study examined the hypothesis that training to a presumably postsynaptic dose of QUIN (0.20 mg/kg) would produce the opposite pattern of effects. Using drug discrimination procedures, substitution for 0.05 mg/kg (28), but not 0.20 mg/kg QUIN, was produced by the D-1 antagonist SCH23390, the catecholamine depleter alpha-methyl-paratyrosine and low doses of apomorphine (up to 0.25 mg/kg). The D-2 agonist NPA substituted fully for 0.05 but only partially for 0.20 mg/kg QUIN. Cocaine and d-amphetamine (alone or with SCH 23390) substituted only minimally for either QUIN training dose. The putative D-3 agonist 7-OH-DPAT engendered primarily saline responding when substituted for 0.20 QUIN. The 0.20 QUIN stimulus was antagonized by the D-2 blocker haloperidol and partially blocked by the Dt antagonist SCH 23390. These data show a clear difference in the mediation of the stimulus properties of a low (0.05 mg/kg) vs. a high (0.20 mg/kg) dose of QUIN and are suggestive of a preferential postsynaptic D-2 mediation of the 0.20 mg/kg QUIN dose. Copyright (C) 1996 Elsevier Science Inc.