Title: Apparent mediation of the stimulus properties of a low dose of quinpirole by dopaminergic autoreceptors.

Authors: Widzowski, D V; Cory-Slechta, D A

Published In J Pharmacol Exp Ther, (1993 Aug)

Abstract: This study examined the hypothesis that, if the stimulus properties of the D2 agonist quinpirole (QUIN) were mediated by autoreceptors, then pharmacological treatments engendering a decline in dopamine (DA) release and consequent decrease in postsynaptic DA receptor stimulation should result in QUIN-appropriate responding; those that activate postsynaptic receptors should result in saline-appropriate responding. In rats trained to discriminate 0.05 mg/kg of QUIN from saline using standard operant drug discrimination procedures, QUIN (up to the training dose), two other putative D2 autoreceptor agonists (low-dose apomorphine and N-propylnorapomorphine), the DA depeleter alpha-methyl-p-tyrosine (AMPT) and the D1 antagonist SCH 23390 all produced primarily QUIN-lever responding. Moreover, coadministration of alpha-methyl-p-tyrosine with QUIN potentiated QUIN-stimulus properties. Higher doses of apomorphine, known to stimulate postsynaptic D1 and D2 receptors and pretreatment with the D2 antagonist haloperidol decreased QUIN-lever responding. Neither the D1 agonist SKF38393, the indirect D1/D2 agonist d-amphetamine, the D2 antagonist haloperidol or coadministration of SCH 23390 and d-amphetamine substituted for QUIN. Coadministration of either SKF 38393 or d-amphetamine with QUIN decreased levels of QUIN responding. Taken together, the data are consistent with the contention that the stimulus properties of 0.05 mg/kg of QUIN are primarily mediated by D2-type presynaptic autoreceptors and that these stimulus properties involve a decline in DA release and consequent decreased postsynaptic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

PubMed ID: 8355188

MeSH Terms: No MeSH terms associated with this publication