Bamford Nigel S, Zhang Hui, Joyce John A, Scarlis Christine A, Hanan Whitney, Wu Nan-Ping, André Véronique M, Cohen Rachel, Cepeda Carlos, Levine Michael S, Harleton Erin, Sulzer David
Department of Neurology, University of Washington, Seattle, WA 98105, USA.
Neuron. 2008 Apr 10;58(1):89-103. doi: 10.1016/j.neuron.2008.01.033.
Addiction-associated behaviors such as drug craving and relapse are hypothesized to result from synaptic changes that persist long after withdrawal and are renormalized by drug reinstatement, although such chronic synaptic effects have not been identified. We report that exposure to the dopamine releaser methamphetamine for 10 days elicits a long-lasting (>4 month) depression at corticostriatal terminals that is reversed by methamphetamine readministration. Both methamphetamine-induced chronic presynaptic depression and the drug's selective renormalization in drug-experienced animals are independent of corresponding long-term changes in synaptic dopamine release but are due to alterations in D1 dopamine and cholinergic receptor systems. These mechanisms might provide a synaptic basis that underlies addiction and habit learning and their long-term maintenance.
成瘾相关行为，如药物渴望和复发，被认为是由戒断后长期持续的突触变化引起的，并且通过药物复吸可使其恢复正常，尽管尚未确定这种慢性突触效应。我们报告，暴露于多巴胺释放剂甲基苯丙胺10天会在皮质纹状体终末引发持久（>4个月）的抑制，而甲基苯丙胺再次给药可使其逆转。甲基苯丙胺诱导的慢性突触前抑制以及该药物在有药物使用经历的动物中的选择性恢复正常，均与突触多巴胺释放的相应长期变化无关，而是由于D1多巴胺和胆碱能受体系统的改变所致。这些机制可能为成瘾、习惯学习及其长期维持提供突触基础。
