The effects of dopamine agonists on fixed interval schedule-controlled behavior are selectively altered by low-level lead exposure.
A previous report of differential effects of catecholaminergic compounds, but not other classes of compounds, on FI (fixed interval) response rates of lead (Pb)-treated pigeons suggests that catecholamine system disturbances might play a role in lead (Pb)-induced changes in FI performance. The current study sought to extend those findings using more selective dopaminergic (DA) D1 and D2-like receptor agonists, Pb-treated rats, and additional classes of compounds. Drug-induced changes in FI performance of rats exposed chronically from weaning to 0, 50, or 150 ppm Pb acetate in drinking water were compared following the administration of drugs known to impact various neurotransmitter systems altered by Pb exposure, including the selective D2-like agonist quinpirole, the D1 agonists SKF38393 and SKF82958, the mu-opioid agonist morphine, the muscarinic cholinergic agonist arecoline, the glutamate agonist NMDA, and the noncompetitive NMDA antagonist MK-801. All drugs except NMDA significantly altered FI performance, but only the effects of DA agonists differed in control and Pb-exposed rats. Pb exposure attenuated the decrements in rates produced by D1 agonists and at 150 ppm modestly altered the rate changes associated with low doses of quinpirole. These data demonstrate functional DA alterations in response to Pb exposure and provide further evidence for the selective involvement of such effects in FI performance.
Cory-Slechta
D A
DA
Department of Neurobiology, University of Rochester School of Medicine & Dentistry, NY 14642, USA. slechta@envmed.rochester.edu
Pokora
M J
MJ
Preston
R A
RA
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001115:Arecoline / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D010856:Columbidae; D003216:Conditioning, Operant / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007855:Lead Poisoning / Q000523:psychology*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D012054:Reinforcement, Psychology
D001552:Benzazepines; D018491:Dopamine Agonists; D019257:Quinpirole; D001115:Arecoline; D016202:N-Methylaspartate; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D009020:Morphine; C071262:SK&F 82958