Modulation of sensitivity to alcohol by cortical and thalamic brain regions
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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‐FosIRin themPFC,IC, Rh and AcbC. Lastly, site‐specific pharmacological inactivation with muscimol + baclofen (GABAAagonist + GABABagonist) was used to determine the functional role of themPFC,ICand Rh in modulating the interoceptive effects of alcohol in rats trained to discriminate alcohol (1 g/kg,IG) vs. water.mPFCinactivation resulted in full substitution for the alcohol training dose, andICand 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.
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Noncontingent alcohol exposure inhibits aIC activity.
“Noncontingent alcohol exposure has been demonstrated to inhibit aIC activity”
From The Insula: A Brain Stimulation Target for the Treatment of Addiction (2019) · cites this paper as Jaramillo et al., 2016
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The Insula: A Brain Stimulation Target for the Treatment of Addiction
Ibrahim, C., Rubin-Kahana, D. S., Pushparaj, A., Musiol, M., Blumberger, D. M., Daskalakis, Z. J., Zangen, A., & Le Foll, B. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00720 · Cited by 133 · see citing works
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- Authors
- Jaramillo, A. A., Randall, P. A., Frisbee, S., & Besheer, J.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Besheer, Joyce
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2016-09-08
- Volume
- 44
- Issue
- 8
- Pages
- 2569-2580
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- PMC
- PMC5377065
- OpenAlex
- W2515371583
- Cited by
- 42
- References
- 80
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 4 · 2022: 4 · 2021: 6 · 2020: 9 · 2019: 5 · 2018: 4 · 2017: 5
- FWCI
- 2.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institute on Alcohol Abuse and Alcoholism (AA019682)
- National Science Foundation (DGE‐1144081)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- alcohol sensitivity, nucleus accumbens core, medial prefrontal cortex, insula, c-Fos immunoreactivity, afferent projections
- MeSH terms
- Ethanol, Animals, Behavior, Animal, Discrimination Learning, Male, Muscimol, Thalamus, Proto-Oncogene Proteins c-fos, Rats, Long-Evans
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