D1 Dopamine Receptor-Mediated LTP at GABA Synapses Encodes Motivation to Self-Administer Cocaine in Rats
D1 Dopamine Receptor-Mediated LTP at GABA Synapses Encodes Motivation to Self-Administer Cocaine in Rats
复制标题
DOI：
10.1523/jneurosci.1784-13.2013
复制
发表时间：
2013-07-17
影响因子：
5.3
通讯作者：
Dumont, Eric C.
中科院分区：
文献类型：
--
作者：
Krawczyk, Michal;Mason, Xenos;Dumont, Eric C.
增强的吸毒动机是成瘾的一个核心特征，但这种适应不良行为的神经基础仍然是未知的。在这里，我们报告了一种D1样多巴胺受体（DRD 1）介导的GABA（A）-IPSCs（D1-LTPGABA）在终纹卵圆床核的长时程增强，这与大鼠自我给予可卡因的动机呈正相关。同样，在体内终纹卵圆床内核DRD 1药理学阻断可以更有效地减少大鼠对可卡因的杠杆按压，从而增强对可卡因的动机。D1-LTPGABA导致增强的功能和表达的G-蛋白-非依赖性DRD 1偶联c-Src酪氨酸激酶，并需要局部释放神经降压素。有没有D1-LTPGABA在大鼠自我管理的蔗糖，在那些有限的可卡因自我管理的经验，或在那些被动地接受可卡因（轭）。因此，我们的研究揭示了一种新的神经生理学机制，有助于个人的动机，自我管理可卡因，一个关键的精神生物学因素的强迫性药物使用和成瘾。
Enhanced motivation to take drugs is a central characteristic of addiction, yet the neural underpinning of this maladaptive behavior is still largely unknown. Here, we report a D1-like dopamine receptor (DRD1)-mediated long-term potentiation of GABA(A)-IPSCs (D1-LTPGABA) in the oval bed nucleus of the stria terminalis that was positively correlated with motivation to self-administer cocaine in rats. Likewise, in vivo intra-oval bed nucleus of the stria terminalis DRD1 pharmacological blockade reduced lever pressing for cocaine more effectively in rats showing enhanced motivation toward cocaine. D1-LTPGABA resulted from enhanced function and expression of G-protein-independent DRD1 coupled to c-Src tyrosine kinases and required local release of neurotensin. There was no D1-LTPGABA in rats that self-administered sucrose, in those with limited cocaine self-administration experience, or in those that received cocaine passively (yoked). Therefore, our study reveals a novel neurophysiological mechanism contributing to individual motivation to self-administer cocaine, a critical psychobiological element of compulsive drug use and addiction.