Molecular and Integrative Neurosciences Department, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, California 92037, USA.
Prog Neuropsychopharmacol Biol Psychiatry. 2009 Nov 13;33(8):1347-55. doi: 10.1016/j.pnpbp.2009.08.003. Epub 2009 Aug 12.
The juxtacapsular nucleus of the anterior division of the BNST (jcBNST) receives robust glutamatergic projections from the basolateral nucleus of the amygdala (BLA), the postpiriform transition area, and the insular cortex as well as dopamine (DA) inputs from the midbrain. In turn the jcBNST sends GABAergic projections to the medial division of the central nucleus of the amygdala (CEAm) as well as other brain regions. We recently described a form of long-term potentiation of the intrinsic excitability (LTP-IE) of neurons of the juxtacapsular nucleus of BNST (jcBNST) in response to high-frequency stimulation (HFS) of the stria terminalis that was impaired during protracted withdrawal from alcohol, cocaine, and heroin and in rats chronically treated with corticotropin-releasing factor (CRF) intracerebroventricularly. Here we show that DAergic neurotransmission is required for the induction of LTP-IE of jcBNST neurons through dopamine (DA) D1 receptors. Thus, activation of the central CRF stress system and altered DAergic neurotransmission during protracted withdrawal from alcohol and drugs of abuse may contribute to the disruption of LTP-IE in the jcBNST. Impairment of this form of intrinsic neuronal plasticity in the jcBNST could result in inadequate neuronal integration and reduced inhibition of the CEA, contributing to the negative affective state that characterizes protracted abstinence in post-dependent individuals. These results provide a novel neurobiological target for vulnerability to alcohol and drug dependence.
BNST 前部分的近壳核（jcBNST）从前杏仁核的外侧核（BLA）、后梨状皮质过渡区和岛叶皮质接收强烈的谷氨酸能投射，以及从中脑来的多巴胺（DA）输入。反过来，jcBNST 向杏仁核中央核的内侧部分（CEAm）以及其他脑区发送 GABA 能投射。我们最近描述了一种 BNST 近壳核（jcBNST）神经元内在兴奋性（LTP-IE）的长期增强形式，这种增强是对终纹床核的高频刺激（HFS）的反应，在酒精、可卡因和海洛因的长期戒断期间以及在慢性给予脑啡肽释放因子（CRF）的大鼠中受损。在这里，我们表明 DA 能神经传递是通过多巴胺（DA）D1 受体诱导 jcBNST 神经元的 LTP-IE 所必需的。因此，在酒精和滥用药物的长期戒断期间，中枢 CRF 应激系统的激活和 DA 能神经传递的改变可能导致 jcBNST 中的 LTP-IE 中断。jcBNST 中这种内在神经元可塑性的损伤可能导致神经元整合不足和对 CEA 的抑制减少，导致依赖后个体长期戒断的特征性负性情感状态。这些结果为易患酒精和药物依赖的神经生物学靶点提供了新的依据。
