Optogenetic control of alcohol-seeking behavior via the dorsomedial striatal circuit

NEUROPHARMACOLOGY

卷:155

Article

Hellard, Emily Roltsch¹  Binette, Annalise^1,2  Zhuang, Xiaowen¹  Lu, Jiayi¹  Ma, Tengfei¹  Jones, Bradley^1,2  Williams, Eric¹  Jayavelu, Swetha¹  Wang, Jun^1,2 

[1] Texas A&M Univ, Dept Neurosci & Expt Therapeut, Coll Med, Hlth Sci Ctr, Riverside Pkwy,Suite 2106,Med Res & Educ Bldg, Bryan, TX 77807 USA

[2] Texas A&M Univ, Texas A&M Inst Neurosci, College Stn, TX 77843 USA

关键词: Ethanol;    Dorsomedial striatum;    Optogenetics;    Long-term depression (LTD);    Operant self-administration;    Reinstatement;    NMDA receptor;    Dopamine receptor;    D1;    D2;    Corticostriatal;   

DOI  :  10.1016/j.neuropharm.2019.05.022

来源: Elsevier

【 摘 要 】

Alcohol consumption alters glutamatergic transmission in many brain regions, including the dorsomedial striatum (DMS); this aberrant plasticity is thought to be responsible for alcohol-seeking behavior. Recent studies reported that alcohol induced such plasticity specifically in direct pathway spiny projection neurons (dSPNs) of the DMS. However, it is unknown how this specific change contributes to alcohol-seeking behavior and relapse. Here, we first demonstrated that operant alcohol self-administration increased NMDA receptor activity in DMS dSPNs. Next, we. found that optogenetic inhibition of dSPN5 reversibly decreased operant lever presses for alcohol and alcohol intake. Furthermore, optogenetic stimulation of corticostriatal inputs at low and moderate frequencies induced reliable LTD in DMS slices. Surprisingly, in vivo delivery of the LTD-inducing protocol increased operant alcohol self-administration; this effect was blocked by a D2R antagonist. Importantly, LTD induction in the presence of both D1 and D2 receptor antagonists produced a long-lasting decrease in operant alcohol self-administration. Our results suggest that suppressing DMS dSPN5 activity and their cortical inputs represents a novel treatment mechanism for alcohol use disorder.

【 授权许可】

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