Alterations in the biochemical properties of central dopamine synapses following chronic postnatal PbCO3 exposure.
Behavioral studies on spontaneous and stimulant-induced locomotor activity after chronic low-level lead (Pb) exposure prompted us to investigate the pre- and postjunctional biochemical properties at central dopamine (DA) synapses. Rat pups were chronically exposed from birth to 40 ppm of Pb and tested behaviorally and biochemically at 25 to 35 days of age. Pb-exposed rat pups demonstrated locomotor hyperactivity, but the locomotor response to d-amphetamine SO4 (0.5-2.0 mg/kg) or apomorphine HCL (0.5-5.0 mg/kg) was attenuated. Correlative biochemical studies in rat brain tissue demonstrated associated pre- and postjunctional changes at central DA synapses. These biochemical changes included 1) diminished KC-evoked release of exogenous [3H]DA from brain slices, and 2) suppression of the DA receptor-mediated activation of adenylate cyclase in neostriatal homogenates. No changes were observed in the synthesis, accumulation of d-amphetamine-induced release of radiolabeled DA in brain tissue from these animals. These results are discussed in relation to the possible mechanisms associated with Pb-evoked neurochemical changes as well as the role that each of these effects may play in the Pb-induced alterations of locomotor activity.
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002908:Chronic Disease; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D007855:Lead Poisoning / Q000378:metabolism* / Q000503:physiopathology; D009043:Motor Activity / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism
D011189:Potassium Chloride; D003913:Dextroamphetamine; D004298:Dopamine