Stroke triggers nigrostriatal plasticity and increases alcohol consumption in rats

Cathy C.Y. Huang, Tengfei Ma, Emily A. Roltsch Hellard, Xuehua Wang, Amutha Selvamani, Jiayi Lu, Farida Sohrabji, Jun Wang

研究成果: 雜誌貢獻期刊論文同行評審

17 引文 斯高帕斯(Scopus)

摘要

Excessive alcohol consumption is a known risk factor for stroke, but the effect of stroke on alcohol intake is unknown. The dorsomedial striatum (DMS) and midbrain areas of the nigrostriatal circuit are critically associated to stroke and alcohol addiction. Here we sought to explore the influence of stroke on alcohol consumption and to uncover the underlying nigrostriatal mechanism. Rats were trained to consume alcohol using a two-bottle choice or operant self-administration procedure. Retrograde beads were infused into the DMS or midbrain to label specific neuronal types, and ischemic stroke was induced in the dorsolateral striatum (DLS). Slice electrophysiology was employed to measure excitability and synaptic transmission in DMS and midbrain neurons. We found that ischemic stroke-induced DLS infarction produced significant increases in alcohol preference, operant self-administration, and relapse. These increases were accompanied by enhanced excitability of DMS and midbrain neurons. In addition, glutamatergic inputs onto DMS D1-neurons was potentiated, whereas GABAergic inputs onto DMS-projecting midbrain dopaminergic neurons was suppressed. Importantly, systemic inhibition of dopamine D1 receptors attenuated the stroke-induced increase in operant alcohol self-administration. Our results suggest that the stroke-induced DLS infarction evoked abnormal plasticity in nigrostriatal dopaminergic neurons and DMS D1-neurons, contributing to increased post-stroke alcohol-seeking and relapse.

原文???core.languages.en_GB???
文章編號2501
期刊Scientific Reports
7
發行號1
DOIs
出版狀態已出版 - 1 12月 2017

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