Acute exposure to triethyl lead enhances the behavioral effects of dopaminergic agonists: involvement of brain dopamine in organolead neurotoxicity.
Acute exposure to triethyl lead chloride (7.88 mg/kg) enhanced the behavioral effects of both direct- and indirect-acting dopaminergic agonists. Rats treated with lead 1 week before testing exhibited an increased response to the motor stimulant effects of D-amphetamine and apomorphine. The dose-response curves for D-amphetamine (1.25, 2.0, 3.15 and 5.0 mg/kg)- and apomorphine (0.2, 0.5, 1.25 and 2.0 mg/kg)-induced hyperactivity were shifted to the left in the triethyl lead group. Finally, apomorphine (1 mg/kg) produced more stereotypy in rats pretreated with triethyl lead. This enhanced sensitivity to dopaminergic agonists was not due to altered pharmacokinetics of the challenge drugs, since the onset and duration of their behavioral effects were not affected by triethyl lead. Furthermore, the regional distribution and accumulation of D-[3H]amphetamine was not altered by triethyl lead. These data suggest that acute exposure to triethyl lead enhances the responsiveness of dopaminergic processes which contribute to locomotor activity. The involvement of brain dopamine in other aspects of organolead neurotoxicity is discussed.
D000818:Animals; D001058:Apomorphine / Q000633:toxicity; D001927:Brain Diseases / Q000139:chemically induced*; D003913:Dextroamphetamine / Q000633:toxicity; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D007854:Lead / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009942:Organometallic Compounds / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013239:Stereotyped Behavior / Q000139:chemically induced
D009942:Organometallic Compounds; D007854:Lead; C010360:triethyllead; D001058:Apomorphine; D003913:Dextroamphetamine; D004298:Dopamine