Assessment of the role of dopaminergic systems in lead-induced learning impairments using a repeated acquisition and performance baseline.
This study assessed the possibility that changes in dopaminergic function might underlie Pb-induced learning impairments. If so, dopaminergic compounds might be expected to produce differential changes in learning accuracy in control vs. Pb-exposed rats. Therefore, the effects on a multiple schedule of repeated acquisition and performance resulting from acute administration of the D1 agonist SKF38393 (3.0-9.0 mg/kg), the D2 agonist quinpirole (.025-.10 mg/kg), and the catecholamine depleter alpha-methyl-paratyrosine (AMPT; 50-100 mg/kg) were compared in control rats and rats chronically exposed to either 50 or 250 ppm Pb acetate in drinking water from weaning. This schedule required completion of a sequence of 3 responses for reinforcement, with the correct sequence for the learning (RA; repeated acquisition) component changing with each successive session, while the performance (P) component sequence remained constant across sessions. Quinpirole and AMPT showed a somewhat similar pattern of effects: both produced a more pronounced impairment of accuracy in the learning component as compared to the performance component of the schedule, and both decreased RA accuracy primarily by increasing the frequency of skipping errors. In contrast, SKF38393 decreased accuracy equivalently in both the RA and P components of the schedule and decreased RA accuracy primarily by increasing the frequency of perseverative errors. There were, however, no differential effects of these drugs on either accuracy or response rate in the Pb-treated group as compared to controls, providing little support, at least on the basis of this approach, for an involvement of dopamine sensitivity changes in lead-induced learning impairments.
Cohn
J
J
Department of Environmental Medicine, University of Rochester School of Medicine, New York 14642, USA.
Cory-Slechta
D A
DA
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal; D018491:Dopamine Agonists / Q000494:pharmacology*; D004873:Ergolines / Q000494:pharmacology; D007854:Lead / Q000633:toxicity*; D007858:Learning; D008297:Male; D009474:Neurons; D019257:Quinpirole; D051381:Rats; D014443:Tyrosine / Q000031:analogs & derivatives*
D018491:Dopamine Agonists; D004873:Ergolines; D019257:Quinpirole; D007854:Lead; D014443:Tyrosine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine