Methamphetamine induces cytosolic Ca2+ oscillations in the VTA dopamine neurons
Methamphetamine induces cytosolic Ca2+ oscillations in the VTA dopamine neurons
复制标题
甲基苯丙胺诱导 VTA 多巴胺神经元胞浆 Ca2+ 振荡
作者：
K. Uramura;T. Yada;S. Muroya;S. Shioda;Toshihiro Shiratani;M. Takigawa
甲基苯丙胺（METH）会导致类似精神分裂症的精神病。腹侧被盖区（VTA）的多巴胺神经元与精神分裂症和药物滥用有关。本研究探讨了METH对腹侧被盖区多巴胺神经元的直接影响。我们用METH（5 mg/kg/d）或生理盐水处理成年SD大鼠7天，分离单个VTA神经元，并通过测量免疫细胞化学鉴定的多巴胺神经元的胞浆Ca 2+浓度（[Ca 2 +]i）来监测神经元活性。急性给药METH增加[Ca 2 +]i多巴胺神经元从甲基和盐水处理的大鼠和诱导振荡的[Ca 2 +]i多巴胺神经元仅从甲基处理的大鼠。[Ca ~（2+）]i振荡可被无Ca ~（2+）条件和Ca ~（2+）通道阻断剂抑制。结果表明，急性METH增加腹侧被盖区多巴胺神经元中的[Ca 2 +]i，亚慢性METH处理使它们对该药物敏感，导致[Ca 2 +]i振荡的诱导。腹侧被盖区多巴胺神经元的激活可能与METH的精神兴奋作用有关。
Methamphetamine (METH) induces a schizophrenia-like psychosis. The dopamine neurons in the ventral tegmental area (VTA) have been implicated in schizophrenia and drug abuse. The present study investigated direct effects of METH on VTA dopamine neurons. We treated adult SD rats with METH (5 mg/kg/day) or saline for 7 days, isolated single VTA neurons, and monitored neurona activities by measuring cytosolic Ca2+ concentration ([Ca2+]i) in immunocytochemically identified dopamine neurons. Acutely administered METH increased [Ca2+]i in dopamine neurons from METH-and saline-treated rats and induced oscillations of [Ca2+]i in dopamine neurons only from METH-treated rats. The METH-induced [Ca2+]i oscillations were inhibited by Ca2+-free conditions and Ca2+ channel blockers. The results indicate that acute METH increases [Ca2+]i in VTA dopamine neurons and that subchronic METH treatment sensitizes them to this drug, resulting in induction of [Ca2+]i oscillations. The activation of VTA dopamine neurons may be related to psycho-stimulant effects of METH.