Uramura K, Yada T, Muroya S, Shioda S, Shiratani T, Takigawa M
Department of Physiology, Faculty of Medicine, Kagoshima University, Japan.
Neuroreport. 2000 Apr 7;11(5):1057-61. doi: 10.1097/00001756-200004070-00031.
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 neuronal 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 Ca(2+)-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.
甲基苯丙胺（METH）会诱发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。本研究调查了METH对VTA多巴胺神经元的直接影响。我们用METH（5毫克/千克/天）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中的胞质Ca2+浓度（[Ca2+]i）来监测神经元活动。急性给予METH会增加METH处理组和生理盐水处理组大鼠多巴胺神经元中的[Ca2+]i，并且仅在METH处理组大鼠的多巴胺神经元中诱导[Ca2+]i振荡。METH诱导的[Ca2+]i振荡在无Ca2+条件和Ca2+通道阻滞剂作用下受到抑制。结果表明，急性METH会增加VTA多巴胺神经元中的[Ca2+]i，并且亚慢性METH处理会使它们对该药物敏感，从而导致[Ca2+]i振荡的诱导。VTA多巴胺神经元的激活可能与METH的精神刺激作用有关。
