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. 2020 Nov 5;10:19178. doi: 10.1038/s41598-020-76183-2

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Inhibition of NAc D2-MSNs in Drd2-iCre rats promotes alcohol intake. (a) Timeline of DMSO and CNO administration. Sessions 19–21: DMSO was administered 30-min before the start of each alcohol session, and bottles were weighed 1-, 4-, and 24-h after the start of drinking. Session 22: CNO was administered to the same rats that received DMSO during sessions 19–21 30-min before the start of drinking, and bottles were weighed 1-, 4-, and 24-h later. (b) Drd2-iCre rats expressing hM3Dq DREADD showed no change in alcohol intake after CNO administration across all time points. Females drank significantly more alcohol than males at 1- and 4-h after the start of drinking. (c) Drd2-iCre male rats expressing the hM4Di DREADD displayed a significant increase in alcohol intake 1-h after CNO administration. Drd2-iCre female rats with the hM4Di DREADD displayed a significant increase in alcohol intake 1- and 4-h after CNO administration. CNO increased alcohol intake overall at the 24-h time point. Drd2-iCre females expressing hM4Di drank significantly more alcohol after CNO administration, but not DMSO, 1- and 4-h after the start of alcohol drinking. (d,e) CNO administration did not alter total fluid intake across any time point in Drd2-iCre rats compared to total fluid intake after DMSO administration. (f, left.) Drd2-iCre rats with the hM3Dq DREADD were no different than Wt rats for percent change in alcohol intake after CNO. (f, right.) Collapsed by sex, Drd2-iCre rats expressing hM4Di showed significant increases in percent change in alcohol intake compared to Wt receiving hM4Di 1- and 4-h after the start of alcohol-drinking. In male rats, Drd2-iCre showed significant increases in percent change in alcohol intake compared to Wt with the hM4Di DREADD 1-h after the start of drinking. Increased percent change in alcohol intake after CNO among Drd2-iCre female rats expressing hM4Di persisted for 24-h after the start of alcohol intake compared to Wt with hM4Di. Data represented as mean ± SEM. (b–e) treatment effects *p < 0.05, **p < 0.01, ***p < 0.001; sex effects ^#p < 0.05, ^##p < 0.01, ^###p < 0.001. (f) Females *p < 0.05, **p < 0.01, ***p < 0.001; Males ^^^p < 0.001.