Apparent mediation of the stimulus properties of a low dose of quinpirole by dopaminergic autoreceptors.
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)
Widzowski
D V
DV
Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, New York.
Cory-Slechta
D A
DA
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
D004873:Ergolines; D008781:Methyltyrosines; D011954:Receptors, Dopamine; D019257:Quinpirole; D019805:alpha-Methyltyrosine; D001058:Apomorphine