Wince L C, Donovan C A, Azzaro A J
J Pharmacol Exp Ther. 1980 Sep;214(3):642-50.
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.
慢性低水平铅(Pb)暴露后对自发和刺激诱导的运动活动的行为学研究促使我们研究中枢多巴胺(DA)突触的突触前和突触后生化特性。将新生大鼠幼崽从出生开始长期暴露于40 ppm的铅中,并在25至35日龄时进行行为学和生化测试。暴露于铅的大鼠幼崽表现出运动活动亢进,但对硫酸右苯丙胺(0.5 - 2.0 mg/kg)或盐酸阿扑吗啡(0.5 - 5.0 mg/kg)的运动反应减弱。对大鼠脑组织进行的相关生化研究表明,中枢DA突触处存在相关的突触前和突触后变化。这些生化变化包括:1)钾离子(K⁺)诱发的脑片中外源性[³H]DA释放减少;2)新纹状体匀浆中DA受体介导的腺苷酸环化酶激活受到抑制。在这些动物的脑组织中,未观察到放射性标记DA的合成、蓄积以及右旋苯丙胺诱导释放的变化。本文将结合与铅诱发神经化学变化相关的可能机制以及这些效应在铅诱导的运动活动改变中可能发挥的作用来讨论这些结果。