DeHaven-Hudkins D L, Schulz D W, Walsh T J, Mailman R B
Biological Sciences Research Center, University of North Carolina School of Medicine, Chapel Hill 27514.
Neurotoxicol Teratol. 1988 Jul-Aug;10(4):279-85. doi: 10.1016/0892-0362(88)90029-3.
Rats treated with triethyllead (TEL) exhibit a behavioral supersensitivity to challenge with dopamine agonists at 7 days following administration of TEL. In the present series of experiments, some neurochemical mechanisms which may affect this behavioral supersensitivity were detected. Administration of a single dose of TEL chloride (7.88 mg/kg, SC) to male Fischer-344 rats decreased the concentrations of dopamine in hippocampus, and of serotonin in olfactory tubercle, at Day 7 posttreatment. The ratio of 5-hydroxyindoleacetic acid/5-hydroxytryptamine (one estimate of serotonin turnover) was increased in nucleus accumbens (p less than 0.05), with a similar trend in olfactory tubercle and striatum (p less than 0.10). No changes were detected in binding of [3H]spiperone to D2 dopamine receptors in striatum or olfactory tubercle. However, although basal adenylate cyclase activity was unaltered in TEL-treated rats, the Vmax for dopamine-stimulated adenylate cyclase activity was significantly elevated in olfactory tubercle. Conversely, TEL at micromolar concentrations markedly attenuated both basal and dopamine-stimulated adenylate cyclase activity in vitro in striatal homogenates. These data suggest the hypothesis that administration of TEL to rats results in an up-regulation of D1 dopamine receptors in olfactory tubercle, and that the behavioral supersensitivity of TEL-treated animals to dopamine agonists may, in part, be a result of this receptor supersensitivity.
用三乙基铅（TEL）处理的大鼠在给予TEL后7天，对多巴胺激动剂的激发表现出行为超敏反应。在本系列实验中，检测到了一些可能影响这种行为超敏反应的神经化学机制。给雄性Fischer-344大鼠单次皮下注射氯化TEL（7.88毫克/千克）后，在处理后第7天，海马体中的多巴胺浓度以及嗅结节中的血清素浓度降低。伏隔核中5-羟吲哚乙酸/5-羟色胺的比率（血清素周转率的一种估计）升高（p小于0.05），嗅结节和纹状体中也有类似趋势（p小于0.10）。纹状体或嗅结节中[3H]螺哌隆与D2多巴胺受体的结合未检测到变化。然而，尽管TEL处理的大鼠基础腺苷酸环化酶活性未改变，但嗅结节中多巴胺刺激的腺苷酸环化酶活性的Vmax显著升高。相反，微摩尔浓度的TEL在体外显著减弱了纹状体匀浆中的基础和多巴胺刺激的腺苷酸环化酶活性。这些数据提出了一个假设，即给大鼠施用TEL会导致嗅结节中D1多巴胺受体上调，并且TEL处理的动物对多巴胺激动剂的行为超敏反应可能部分是这种受体超敏反应的结果。
