Functional role for cortical-striatal circuitry in modulating alcohol self-administration

NEUROPHARMACOLOGY

卷:130

Article

Jaramillo, Anel A.^1,2  Randall, Patrick A.¹  Stewart, Spencer¹  Fortino, Brayden¹  Van Voorhies, Kalynn¹  Besheer, Joyce^1,2,3 

[1] Univ N Carolina, Bowles Ctr Alcohol Studies, Thurston Bowles Bldg,CB 7178, Chapel Hill, NC 27599 USA

[2] Univ N Carolina, Neurosci Curriculum, Chapel Hill, NC 27599 USA

[3] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA

关键词: Alcohol;    Insular cortex;    Medial prefrontal cortex;    Nucleus accumbens core;    Reinforcement;    Self-administration;   

DOI  :  10.1016/j.neuropharm.2017.11.035

来源: Elsevier

【 摘 要 】

The cortical-striatal brain circuitry is heavily implicated in drug-use. As such, the present study investigated the functional role of cortical-striatal circuitry in modulating alcohol self-administration. Given that a functional role for the nucleus accumbens core (AcbC) in modulating alcohol-reinforced responding has been established, we sought to test the role of cortical brain regions with afferent projections to the AcbC: the medial prefrontal cortex (mPFC) and the insular cortex (IC). Long-Evans rats were trained to self-administer alcohol (15% alcohol (v/v)+2% sucrose (w/v)) during 30 min sessions. To test the functional role of the mPFC or IC, we utilized a chemogenetic technique (hM4Di-Designer Receptors Activation by Designer Drugs) to silence neuronal activity prior to an alcohol self-administration session. Additionally, we chemogenetically silenced mPFC -> AcbC or IC -> AcbC projections, to investigate the role of cortical-striatal circuitry in modulating alcohol self-administration. Chemogenetically silencing the mPFC decreased alcohol self-administration, while silencing the IC increased alcohol self-administration, an effect absent in mCherry-Controls. Interestingly, silencing mPFC -> AcbC projections had no effect on alcohol self-administration. In contrast, silencing IC -> AcbC projections decreased alcohol self-administration, in a reinforcer-specific manner as there was no effect in rats trained to self-administer sucrose (0.8%, w/v). Additionally, no change in self-administration was observed in the mCherry-Controls. Together these data demonstrate the complex role of the cortical-striatal circuitry while implicating a role for the insula-striatal circuit in modulating ongoing alcohol self-administration. (C) 2017 Elsevier Ltd. All rights reserved.

【 授权许可】

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