Preexisting risk-avoidance and enhanced alcohol relief are driven by imbalance of the striatal dopamine receptors in mice
Alcohol use disorder (AUD) is frequently comorbid with anxiety disorders, yet whether alcohol abuse precedes or follows the expression of anxiety remains unclear. Rodents offer control over the first drink, an advantage when testing the causal link between anxiety and AUD. Here, we utilized a risk-avoidance task to determine anxiety-like behaviors before and after alcohol exposure. We found that alcohol's anxiolytic efficacy varied among inbred mice and mice with high risk-avoidance showed heightened alcohol relief. While dopamine D1 receptors in the striatum are required for alcohol's relief, their levels alone were not correlated with relief. Rather, the ratio between striatal D1 and D2 receptors was a determinant factor for risk-avoidance and alcohol relief. We show that increasing striatal D1 to D2 receptor ratio was sufficient to promote risk-avoidance and enhance alcohol relief, even at initial exposure. Mice with high D1 to D2 receptor ratio were more prone to continue drinking despite adverse effects, a hallmark of AUD. These findings suggest that an anxiety phenotype may be a predisposing factor for AUD.
Authors
- Emilya Ventriglia (ORCID: https://orcid.org/0000-0001-5077-5443)
- Veronica A. Alvarez (ORCID: https://orcid.org/0000-0003-2611-8675)
- Hannah C Goldbach (ORCID: https://orcid.org/0000-0002-5697-4694)
- Patrick Hong (ORCID: https://orcid.org/0000-0002-3701-1497)
- Marilyn Bravo (ORCID: https://orcid.org/0000-0003-1817-6461)
- Jordi Bonaventura (ORCID: https://orcid.org/0000-0002-4745-0151)
- Lucy Anderson (ORCID: https://orcid.org/0000-0002-8908-2887)
- Dennis A. Burke (ORCID: https://orcid.org/0000-0002-7515-4093)
- Erin M. Murray (ORCID: https://orcid.org/0000-0003-4179-7717)
- Han Bin Kwon
- Miriam E. Bocarsly (ORCID: https://orcid.org/0000-0001-9217-032X)
- Roland Bock (ORCID: https://orcid.org/0000-0002-8654-1080)
- Michael Michaelides (ORCID: https://orcid.org/0000-0003-0398-4917)
- Catherine E. Teresi
- Rishi Raman
- Marlisa Shaw
- Imran Khawaja (ORCID: https://orcid.org/0000-0003-4148-119X)
Institutions
- Rutgers, The State University of New Jersey (US)
- National Institutes of Health (US)
- National Institute on Drug Abuse (US)
- National Institute on Alcohol Abuse and Alcoholism (US)
- Office of Research Services (US)
- National Institute of Mental Health (US)
- National Institute of Mental Health (CZ)
- Rutgers New Jersey Medical School (US)
- Universitat de Barcelona (ES)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-10-22
- DOI
- https://doi.org/10.1038/s41467-024-53414-y
- Citations
- 5
- Primary Topic
- Neurotransmitter Receptor Influence on Behavior
- Type
- article
- Field-Weighted Citation Impact
- 1.34
Funders
- National Institutes of Health