Department of Basic Neurosciences, Medical Faculty, University of Geneva, CH-1211 Geneva, Switzerland.
Science. 2013 Sep 27;341(6153):1521-5. doi: 10.1126/science.1237059.
Drug-evoked synaptic plasticity in the mesolimbic system reshapes circuit function and drives drug-adaptive behavior. Much research has focused on excitatory transmission in the ventral tegmental area (VTA) and the nucleus accumbens (NAc). How drug-evoked synaptic plasticity of inhibitory transmission affects circuit adaptations remains unknown. We found that medium spiny neurons expressing dopamine (DA) receptor type 1 (D1R-MSNs) of the NAc project to the VTA, strongly preferring the GABA neurons of the VTA. Repeated in vivo exposure to cocaine evoked synaptic potentiation at this synapse, occluding homosynaptic inhibitory long-term potentiation. The activity of the VTA GABA neurons was thus reduced and DA neurons were disinhibited. Cocaine-evoked potentiation of GABA release from D1R-MSNs affected drug-adaptive behavior, which identifies these neurons as a promising target for novel addiction treatments.
药物诱发的中脑边缘系统中的突触可塑性重塑了电路功能，并驱动了药物适应性行为。大量研究集中在腹侧被盖区（VTA）和伏隔核（NAc）中的兴奋性传递。药物诱发的抑制性传递的突触可塑性如何影响电路适应仍然未知。我们发现，表达多巴胺（DA）受体 1 型（D1R-MSNs）的 NAc 的中间神经元投射到 VTA，强烈偏好 VTA 的 GABA 神经元。在体内反复接触可卡因会在这个突触上引起突触增强，阻断同源抑制性长时程增强。因此，VTA GABA 神经元的活动减少，DA 神经元被去抑制。D1R-MSNs 释放 GABA 的可卡因诱导增强作用影响药物适应性行为，这表明这些神经元是新型成瘾治疗的一个有前途的靶点。
