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. 2021 Sep 28;26(12):7403–7416. doi: 10.1038/s41380-021-01304-w

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© The Author(s) 2021

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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — a Mice with a heterozygous NSM knock out (fro) show reduced alcohol consumption in a two-bottle free-choice paradigm compared to wild type (WT) controls. b Lack of NSM function did not affect total fluid consumption in mice. Data are expressed as means ± s.e.m. (n = 8 per group; **P < 0.001; ****P < 0.001 vs. WT). c Alcohol drinking was reduced in C57Bl6J mice in a two-bottle free-choice drinking test by repeated treatment with the NSM inhibitor ES048 (i.p., grey arrows). d No effect of the ES048 treatment was observed on water consumption in these animals. Data are expressed as means ± s.e.m. (n = 10 per group; *P < 0.05; **P < 0.01 vs. vehicle control). e No role of NSM in taste preference. f, g Free-choice alcohol drinking yielded a proportional blood alcohol concentration (BAC) in heterozygous NSM deficient mice (fro) and wild type (WT) mice at individual level (n = 7 per group). h No difference in BAC after bolus injection of alcohol (3g/kg, i.p) in fro and WT mice (n = 9–10 per group). i, j Lack of NSM function has no effect on the sedating properties in the loss of the rightening reflex (LORR) of a single alcohol injection (3.5 g/kg; i.p.) as shown in latency and duration of sedating effects (n = 9 per group). k NSM has no role in the establishment of the conditioned reinforcing effects of alcohol in mice in a conditioned place preference (CPP) test, but (l) is required for locomotor activating effects of alcohol (2 g/kg, i.p.; Bl baseline, T test trial). Data are expressed as means ± s.e.m. (n = 11–15 per group; ^$P < 0.05, vs. BL). m NSM is not involved in the expression of the conditioned reinforcing and conditioned locomotor effects of alcohol in mice as the two NSM inhibitors GW4869 and ES048 applied before CPP retrieval, did not affect CPP expression or (n) conditioned locomotor effects. Data are expressed as means ± s.e.m. (n = 9–10 per group; ***P < 0.01, ANOVA, effect of test trial).