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Preexisting risk-avoidance and enhanced alcohol relief are driven by imbalance of the striatal dopamine receptors in mice

A mouse and a beer bottleHot Off the Press – January, 2025

Published in Nature Communications by Miriam Bocarsly, Mike Michaelides and Veronica Alvarez, et al. of the NIDA IRP.

Summary

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.

Publication Information

Bocarsly, Miriam E; Shaw, Marlisa J; Ventriglia, Emilya; Anderson, Lucy G; Goldbach, Hannah C; Teresi, Catherine E; Bravo, Marilyn; Bock, Roland; Hong, Patrick; Kwon, Han Bin; Khawaja, Imran M; Raman, Rishi; Murray, Erin M; Bonaventura, Jordi; Burke, Dennis A; Michaelides, Michael; Alvarez, Veronica A

Preexisting risk-avoidance and enhanced alcohol relief are driven by imbalance of the striatal dopamine receptors in mice Journal Article

In: Nat Commun, vol. 15, no. 1, pp. 9093, 2024, ISSN: 2041-1723.

Abstract | Links

@article{pmid39438478b,
title = {Preexisting risk-avoidance and enhanced alcohol relief are driven by imbalance of the striatal dopamine receptors in mice},
author = {Miriam E Bocarsly and Marlisa J Shaw and Emilya Ventriglia and Lucy G Anderson and Hannah C Goldbach and Catherine E Teresi and Marilyn Bravo and Roland Bock and Patrick Hong and Han Bin Kwon and Imran M Khawaja and Rishi Raman and Erin M Murray and Jordi Bonaventura and Dennis A Burke and Michael Michaelides and Veronica A Alvarez},
url = {https://pubmed.ncbi.nlm.nih.gov/39438478/},
doi = {10.1038/s41467-024-53414-y},
issn = {2041-1723},
year = {2024},
date = {2024-10-01},
urldate = {2024-10-01},
journal = {Nat Commun},
volume = {15},
number = {1},
pages = {9093},
abstract = {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.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

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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.

Close

  • https://pubmed.ncbi.nlm.nih.gov/39438478/
  • doi:10.1038/s41467-024-53414-y

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