Optogenetic induction of orbitostriatal long-term potentiation in the dorsomedial striatum elicits a persistent reduction of alcohol-seeking behavior in rats

NEUROPHARMACOLOGY

卷:191

Article

Cheng, Yifeng^1,2  Xie, Xueyi¹  Lu, Jiayi¹  Gangal, Himanshu¹  Wang, Wei¹  Melo, Sebastian¹  Wang, Xuehua¹  Jerger, Jared¹  Woodson, Kayla¹  Garr, Eric²  Huang, Yufei¹  Janak, Patricia²  Wang, Jun¹ 

[1] Texas A&M Univ, Dept Neurosci & Expt Therapeut, Coll Med, Hlth Sci Ctr, Bryan, TX 77807 USA

[2] Johns Hopkins Univ, Dept Psychol & Brain Sci, Baltimore, MD 21218 USA

关键词: Orbitofrontal cortex;    Dorsomedial striatum;    Synaptic plasticity;    Alcohol;    Optogenetic;    Operant self-administration;    Dopamine D1 receptor;    Adenosine A2A receptor;   

DOI  :  10.1016/j.neuropharm.2021.108560

来源: Elsevier

【 摘 要 】

Uncontrolled drug-seeking and -taking behaviors are generally driven by maladaptive corticostriatal synaptic plasticity. The orbital frontal cortex (OFC) and its projections to the dorsomedial striatum (DMS) have been extensively implicated in drug-seeking and relapse behaviors. The influence of the synaptic plasticity of OFC projections to the DMS (OFC -> DMS) on drug-seeking and -taking behaviors has not been fully characterized. To investigate this, we trained rats to self-administer 20% alcohol and then delivered an in vivo optogenetic protocol designed to induce long-term potentiation (LTP) selectively at OFC -> DMS synapses. We selected LTP induction because we found that voluntary alcohol self-administration suppressed OFC -> DMS transmission and LTP may normalize this transmission, consequently reducing alcohol-seeking behavior. Importantly, ex vivo slice electrophysiology studies confirmed that this in vivo optical stimulation protocol resulted in a significant increase in excitatory OFC -> DMS transmission strength on day two after stimulation, suggesting that LTP was induced in vivo. Rat alcohol-seeking and -taking behaviors were significantly reduced on days 1-3, but not on days 7-11, after LTP induction. Striatal synaptic plasticity is modulated by several critical neurotransmitter receptors, including dopamine D1 receptors (D1Rs) and adenosine A2A receptors (A2ARs). We found that delivery of in vivo optical stimulation in the presence of a D1R antagonist abolished the LTP-associated decrease in alcohol-seeking behavior, whereas delivery in the presence of an A2AR antagonist may facilitate this LTP-induced behavioral change. These results demonstrate that alcohol-seeking behavior was negatively regulated by the potentiation of excitatory OFC -> DMS neurotransmission. Our findings provide direct evidence that the OFC exerts top-down control of alcohol-seeking behavior via the DMS.

【 授权许可】

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