Lead-induced decrements in waiting behavior: involvement of D2-like dopamine receptors.
Some behavioral changes produced by chronic postweaning lead (Pb) exposure have been linked to mesolimbic dopamine (DA) system alterations. This study sought to determine the role of DA systems in Pb-induced changes in a fixed ratio (FR) waiting-for-reward paradigm. Rats exposed chronically from weaning to 0, 50, or 150 ppm Pb acetate drinking solutions earned free reinforcers for waiting after completion of an FR, with increasing time between successive free reinforcers. Responses during the waiting period reset the FR requirement. Once performance stabilized, the effects of acute IP administration of the D1 agonist SKF82958, the D2 agonist quinpirole, the D1 antagonist SCH23390, and the D2 antagonist eticlopride were determined. Pb itself increased FR response rates and decreased mean waiting time, a pattern of behavior that increased the number of earned reinforcers, but doubled the number of responses/reinforcer. None of the DA compounds mimicked Pb effects when administered to controls. Only DA agonists altered waiting behavior and responses per reinforcer. Quinpirole, in particular, appeared to reverse Pb effects on the FR wait baseline by increasing waiting time and decreasing FR resets to control levels. These findings point to a particular role for D2 DA function in Pb's detrimental effects on waiting.
Brockel
B J
BJ
Department of Environmental Medicine, University of Rochester Medical School, NY 14642, USA.
Cory-Slechta
D A
DA
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D007854:Lead / Q000633:toxicity*; D008297:Male; D019257:Quinpirole / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D017447:Receptors, Dopamine D1 / Q000819:agonists; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000187:drug effects*; D012055:Reinforcement Schedule; D012457:Salicylamides / Q000494:pharmacology
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D019257:Quinpirole; D007854:Lead; C071262:SK&F 82958; C045989:eticlopride