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Neuropharmacology. 2018 Mar 1;130:42-53. doi: 10.1016/j.neuropharm.2017.11.035. Epub 2017 Nov 26.

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

Author information

1
Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States; Neuroscience Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
2
Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
3
Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States; Neuroscience Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States; Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States. Electronic address: jbesheer@med.unc.edu.

Abstract

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.

KEYWORDS:

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

PMID:
29183687
PMCID:
PMC5891728
DOI:
10.1016/j.neuropharm.2017.11.035
[Indexed for MEDLINE]
Free PMC Article

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