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PD is often accompanied by other psychiatric conditions, such as anxiety, depression, and drug use disorders, which typically emerge in adulthood. Some of these point mutations, such as <jats:italic>SNCA<\/jats:italic> and <jats:italic>A30T<\/jats:italic>, have been linked to behavioral effects that are not commonly associated with PD, especially regarding alcohol consumption patterns. In this study, we investigated whether the familial PD point mutation <jats:italic>A53T<\/jats:italic> is associated with changes in alcohol consumption behavior and emotional states at ages not yet characterized by \u03b1\u2010synuclein accumulation. The affective and alcohol\u2010drinking phenotypes remained unaltered in female PDGF\u2010hA53T\u2010synuclein\u2010transgenic (A53T) mice during both early and late adulthood. Brain region\u2010specific activation of ceramide\u2010producing enzymes, acid sphingomyelinase (ASM), and neutral sphingomyelinase (NSM), known for their neuroprotective properties, was observed during early adulthood but not in late adulthood. In males, the <jats:italic>A53T<\/jats:italic> mutation was linked to a reduction in alcohol consumption in both early and late adulthood. However, male A53T mice displayed increased anxiety\u2010 and depression\u2010like behaviors during both early and late adulthood. Enhanced ASM activity in the dorsal mesencephalon and ventral hippocampus may potentially contribute to these adverse behavioral effects of the mutation in males during late adulthood. In summary, the <jats:italic>A53T<\/jats:italic> gene mutation was associated with diverse changes in emotional states and alcohol consumption behavior long before the onset of PD, and these effects varied by sex. These alterations in behavior may be linked to changes in brain ceramide metabolism.<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc16051-fig-0009-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1111\/jnc.16051","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T11:10:27Z","timestamp":1706526627000},"page":"269-287","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Sex\u2010specific pleiotropic changes in emotional behavior and alcohol consumption in human \u03b1\u2010synuclein <scp>A53T<\/scp> transgenic mice during early 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