Heusner Carrie L, Hnasko Thomas S, Szczypka Mark S, Liu Yuhong, During Matthew J, Palmiter Richard D
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Brain Res. 2003 Aug 8;980(2):266-74. doi: 10.1016/s0006-8993(03)02986-x.
Administration of amphetamine to mice evokes hyperlocomotion. Dopamine deficient (DD) mice, in which tyrosine hydroxylase (TH) has been specifically inactivated in dopaminergic neurons, have a blunted response to amphetamine, indicating that the hyperlocomotive response requires dopamine. Dopamine production can be restored to specific brain regions by using adeno-associated viruses expressing TH and GTP cyclohydrolase 1 (GTPCH1). Restoration of dopamine specifically to the nucleus accumbens (NAc) of DD mice completely restores the ability of these mice to respond to amphetamine. This response is specific to the dopamine production in the NAc, as restoration of dopamine production to the caudate putamen (CPu) does not fully restore the hyperlocomotive response to amphetamine. These data support previous studies in which accumbal dopamine is required for producing a normal locomotor response to amphetamine and further show that release of dopamine restricted to the NAc is sufficient for this response
给小鼠注射苯丙胺会引发活动亢进。多巴胺缺陷（DD）小鼠中，酪氨酸羟化酶（TH）在多巴胺能神经元中被特异性失活，其对苯丙胺的反应减弱，这表明活动亢进反应需要多巴胺。通过使用表达TH和GTP环化水解酶1（GTPCH1）的腺相关病毒，可以将多巴胺的产生恢复到特定脑区。将多巴胺特异性恢复到DD小鼠的伏隔核（NAc）可完全恢复这些小鼠对苯丙胺的反应能力。这种反应对NAc中的多巴胺产生具有特异性，因为将多巴胺产生恢复到尾状壳核（CPu）并不能完全恢复对苯丙胺的活动亢进反应。这些数据支持了先前的研究，即伏隔核多巴胺是产生对苯丙胺的正常运动反应所必需的，并且进一步表明，仅NAc中多巴胺的释放就足以产生这种反应。
