title: Apparent mediation of the stimulus properties of a low dose of quinpirole by dopaminergic autoreceptors.
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)
authors.affiliation: Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, New York.
authors.forename: D V
authors.initials: DV
authors.lastname: Widzowski
authors.forename: D A
authors.initials: DA
authors.lastname: Cory-Slechta
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000494:pharmacology*; D008781:Methyltyrosines / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D019805:alpha-Methyltyrosine
chemical_list: D004873:Ergolines; D008781:Methyltyrosines; D011954:Receptors, Dopamine; D019257:Quinpirole; D019805:alpha-Methyltyrosine; D001058:Apomorphine