Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL 61802, United States.
Neurotoxicol Teratol. 2013 Jul-Aug;38:6-12. doi: 10.1016/j.ntt.2013.04.005. Epub 2013 Apr 23.
PCBs have long been known to affect dopamine (DA) function in the brain. The current study used an amphetamine behavioral sensitization paradigm in rats developmentally exposed to PCBs. Long-Evans rats were given perinatal exposure to 0, 3, or 6mg/kg/day PCBs and behavioral sensitization to d-amphetamine (AMPH) was assessed in one adult male and female/litter. Non-exposed (control) males showed increasing locomotor activity to repeated injections of 0.5mg/kg AMPH, typical of behavioral sensitization. PCB-exposed males showed greater activation to the initial acute AMPH injection, but sensitization occurred later and was blunted relative to controls. Sensitization in control females took longer to develop than in the males, but no exposure-related differences were observed. Analysis of whole brain and serum AMPH content following a final IP injection of 0.5mg/kg revealed no differences among the exposure groups. Overall, these results indicated developmental PCB exposure can alter the motor-stimulating effects of repeated AMPH injections. Males developmentally exposed to PCBs appeared to be pre-sensitized to AMPH, but quickly showed behavioral tolerance to the same drug dose. Results also revealed the behavioral effect was not due to exposure-induced alterations in AMPH metabolism following PCB exposure.
多氯联苯(PCBs)早已被证实会影响大脑中的多巴胺(DA)功能。本研究使用发育性暴露于 PCBs 的大鼠中的安非他命行为敏化范式。长耳大鼠在围产期接受 0、3 或 6mg/kg/天 PCBs 的暴露,并在一只成年雄性和雌性/窝中评估对 d-安非他命(AMPH)的行为敏化作用。未暴露(对照)雄性对 0.5mg/kg AMPH 的重复注射表现出逐渐增加的运动活性,这是行为敏化的典型表现。暴露于 PCBs 的雄性对初始急性 AMPH 注射表现出更大的激活,但敏化发生较晚且相对于对照组减弱。对照雌性的敏化比雄性发展得更慢,但未观察到与暴露有关的差异。在最后一次腹腔注射 0.5mg/kg 后的整个大脑和血清 AMPH 含量分析中,未发现暴露组之间存在差异。总体而言,这些结果表明发育性 PCB 暴露可以改变重复 AMPH 注射的运动刺激作用。发育性暴露于 PCBs 的雄性似乎对 AMPH 预先敏化,但很快对相同药物剂量表现出行为耐受。结果还表明,行为效应不是由于暴露于 PCBs 后暴露诱导的 AMPH 代谢改变所致。