Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Nat Commun. 2018 Apr 3;9(1):1318. doi: 10.1038/s41467-018-03683-1.
Drugs of abuse, including alcohol, ablate the expression of specific forms of long-term synaptic depression (LTD) at glutamatergic synapses in dorsal striatum (DS), a brain region involved in goal-directed and habitual behaviors. This loss of LTD is associated with altered DS-dependent behavior. Given the role of the µ-opioid receptor (MOR) in behavioral responding for alcohol, we explored the impact of alcohol on various forms of MOR-mediated synaptic depression that we find are differentially expressed at specific DS synapses. Corticostriatal MOR-mediated LTD (mOP-LTD) in the dorsolateral striatum occurs exclusively at inputs from anterior insular cortex and is selectively disrupted by in vivo alcohol exposure. Alcohol has no effect on corticostriatal mOP-LTD in dorsomedial striatum, thalamostriatal MOR-mediated short-term depression, or mOP-LTD of cholinergic interneuron-driven glutamate release. Disrupted mOP-LTD at anterior insular cortex-dorsolateral striatum synapses may therefore be a key mechanism of alcohol-induced neuroadaptations involved in the development of alcohol use disorders.
滥用药物，包括酒精，会使背侧纹状体（DS）中谷氨酸能突触的特定形式的长时程突触抑制（LTD）表达减少，DS 是参与目标导向和习惯性行为的脑区。这种 LTD 的丧失与 DS 依赖行为的改变有关。鉴于 μ-阿片受体（MOR）在酒精行为反应中的作用，我们探讨了酒精对各种形式的 MOR 介导的突触抑制的影响，我们发现这些抑制在特定的 DS 突触中差异表达。背外侧纹状体中的皮质纹状体 MOR 介导的 LTD（mOP-LTD）仅发生在前脑岛皮层传入的输入中，并且可被体内酒精暴露选择性破坏。酒精对背内侧纹状体中的皮质纹状体 mOP-LTD、丘脑纹状体 MOR 介导的短期抑制或胆碱能中间神经元驱动的谷氨酸释放的 mOP-LTD 没有影响。因此，前脑岛皮层-背外侧纹状体突触处 mOP-LTD 的破坏可能是酒精引起的与酒精使用障碍发展有关的神经适应的关键机制。
