biostudies-literatureZaniewska MMinistry of Science and Higher EducationEU H2020 MSCA ITNGerman Academic Exchange Service874https://www.ebi.ac.uk/biostudies/studies/S-EPMC8909500biostudies-literatureUnknown11(5)Indirect evidence supports a link between disrupted serotonin (5-hydroxytryptamine; 5-HT) signaling in the brain and addictive behaviors. However, the effects of hyposerotonergia on ethanol drinking behavior are contradictory. In this study, mice deficient in tryptophan hydroxylase 2 (Tph2-/-), the rate-limiting enzyme of 5-HT synthesis in the brain, were used to assess the role of central 5-HT in alcohol drinking behavior. Life-long 5-HT depletion in these mice led to an increased ethanol consumption in comparison to wild-type animals in a two-bottle choice test. Water consumption was increased in naïve 5-HT-depleted mice. However, exposure of Tph2-/- animals to ethanol resulted in the normalization of water intake to the level of wild-type mice. Tph2 deficiency in mice did not interfere CellsTph2 Gene Expression Defines Ethanol Drinking Behavior in Mice.PMC8909500A07/99669N 953327632/MOB/2011/0Alenina NZaniewska MMosienko VBader MfalseTph2 Gene Expression Defines Ethanol Drinking Behavior in Mice.Indirect evidence supports a link between disrupted serotonin (5-hydroxytryptamine; 5-HT) signaling in the brain and addictive behaviors. However, the effects of hyposerotonergia on ethanol drinking behavior are contradictory. In this study, mice deficient in tryptophan hydroxylase 2 (Tph2-/-), the rate-limiting enzyme of 5-HT synthesis in the brain, were used to assess the role of central 5-HT in alcohol drinking behavior. Life-long 5-HT depletion in these mice led to an increased ethanol consumption in comparison to wild-type animals in a two-bottle choice test. Water consumption was increased in naïve 5-HT-depleted mice. However, exposure of Tph2-/- animals to ethanol resulted in the normalization of water intake to the level of wild-type mice. Tph2 deficiency in mice did not interfere 2022-01-01T00:00:00Z2022 Mar2025-05-18T12:35:12.522Z2025-04-06T12:03:23.966ZS-EPMC89095003526949710.3390/cells11050874