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. 2024 Oct 22;15:9093. doi: 10.1038/s41467-024-53414-y

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© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024

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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Fig. 5 — A Time in the EZM open zones for control (black) and iSPN-Drd2HET (orange) mice after receiving either saline or 1.2 g/kg alcohol (green; i.p.; 2-way ANOVA main effect of alcohol F(1,73) = 2.95, p = 0.09; control mice: saline vs. alcohol t(48) = 3.01, p = 0.004; iSPN-Drd2HET: saline vs. alcohol t(25) = 3.31, p = 0.004, n = 15,26 mice/genotype). EZM cartoon is modified BioRender template license Alvarez, V. (2024) BioRender.com/m14d797. B Normalized time spent on EZM open zones following alcohol relative to time spent following saline for iSPN-Drd2HET (orange) and controls (black) (t-test t(39) = 3.31, p = 0.002, n = 15,26 mice/genotype). C Blood ethanol concentrations (BEC) 10 min after 1.2 g/kg alcohol (i.p.; t-test t(25) = 0.60, p > 0.05, n = 10,17mice/genotype). D iSPN-Drd2HET mice were pretreated with either saline or D1-like antagonist SCH-23390 (0.03 mg/kg; i.p.) then tested on EZM following saline or alcohol (1.2 g/kg; i.p.). E iSPN-Drd2HET mice pretreated with saline showed increased time in EZM open zones after alcohol (2-way ANOVA significant interaction SCH-23390 x Alcohol F(3,41) = 13.5, p < 0.0001; saline versus alcohol: p < 0.05, n = 9,12 mice/group), while mice pretreated with SCH-23390 did not show increased time in EZM open zones after alcohol compared to saline (p > 0.05, n = 11,13 mice/group). F iSPN-Drd2HET mice show stronger locomotor response at 2 g/kg alcohol than littermate controls (RM 2-way ANOVA main effect of Genotype F(2,62) = 5.10, p = 0.009; post hoc test p = 0.011, n = 10,23 mice/genotype). G Summary of EZM performance following saline or 1.2 g/kg alcohol (green shade) for control mice with low and high alcohol stimulation and iSPN-Drd2HET mice (n = 22, 28 control mice and 15 iSPN-Drd2HET mice). H Voluntary alcohol consumption in group-housed, intermittent access, operant paradigm. iSPN-Drd2HET (orange) and littermate controls (black) showed similar consumption of alcohol across sessions (RM 2-way ANOVA no effect of Genotype F(11,241) = 0.52, p > 0.05, n = 11,15 mice/genotype). I Water consumption was similar between genotypes on days alcohol was not available (RM 2-way ANOVA no effect of Genotype F(11,263) = 0.74, p > 0.05, n = 11,15 mice/genotype). J Alcohol intake was measured following quinine adulteration (0.5 mM), and normalized to intake before adulteration for iSPN-Drd2HET (orange) and control (black; RM 2-way ANOVA significant interaction Genotype x Quinine: F(1,23) = 4.95, p = 0.036, n = 11,14 mice/genotype). K Percent mice that drop intake during quinine adulteration (adulteration sensitive) and percent that did not drop (adulteration insensitive); two-tailed binomial test of observed findings (iSPN-Drd2HET) vs expected (control) p < 0.01; n = 11,14 mice/genotype). Data presented as mean ± SEM, *p < 0.05, **p < 0.01.