title: Modulation of sensitivity to alcohol by cortical and thalamic brain regions.
abstract: The nucleus accumbens core (AcbC) is a key brain region known to regulate the discriminative stimulus/interoceptive effects of alcohol. As such, the goal of the present work was to identify AcbC projection regions that may also modulate sensitivity to alcohol. Accordingly, AcbC afferent projections were identified in behaviorally naïve rats using a retrograde tracer which led to the focus on the medial prefrontal cortex (mPFC), insular cortex (IC) and rhomboid thalamic nucleus (Rh). Next, to examine the possible role of these brain regions in modulating sensitivity to alcohol, neuronal response to alcohol in rats trained to discriminate alcohol (1 g/kg, intragastric [IG]) vs. water was examined using a two-lever drug discrimination task. As such, rats were administered water or alcohol (1 g/kg, IG) and brain tissue was processed for c-Fos immunoreactivity (IR), a marker of neuronal activity. Alcohol decreased c-Fos IR in the mPFC, IC, Rh and AcbC. Lastly, site-specific pharmacological inactivation with muscimol + baclofen (GABAAagonist + GABABagonist) was used to determine the functional role of the mPFC, IC and Rh in modulating the interoceptive effects of alcohol in rats trained to discriminate alcohol (1 g/kg, IG) vs. water. mPFC inactivation resulted in full substitution for the alcohol training dose, and IC and Rh inactivation produced partial alcohol-like effects, demonstrating the importance of these regions, with known projections to the AcbC, in modulating sensitivity to alcohol. Together, these data demonstrate a site of action of alcohol and the recruitment of cortical/thalamic regions in modulating sensitivity to the interoceptive effects of alcohol.
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Thurston-Bowles Building, CB#7178, Chapel Hill, NC, 27599, USA.|Curriculum in Neurobiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Anel A
authors.initials: AA
authors.lastname: Jaramillo
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Thurston-Bowles Building, CB#7178, Chapel Hill, NC, 27599, USA.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Randall
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Thurston-Bowles Building, CB#7178, Chapel Hill, NC, 27599, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Frisbee
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Thurston-Bowles Building, CB#7178, Chapel Hill, NC, 27599, USA. jbesheer@med.unc.edu.|Curriculum in Neurobiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. jbesheer@med.unc.edu.|Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. jbesheer@med.unc.edu.
authors.forename: Joyce
authors.initials: J
authors.lastname: Besheer
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D009118:Muscimol / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D020318:Rats, Long-Evans; D013788:Thalamus / Q000187:drug effects* / Q000378:metabolism
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D009118:Muscimol; D000431:Ethanol
keywords: addiction; discriminative stimulus; drug-discrimination; interoception