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According to epidemiological and clinical findings, females appear to be more sensitive to the effects of alcohol and thiamine deficiency and have a worse prognosis in recovery from neurocognitive deficits compared with males. This study aimed to characterize the effects of chronic ethanol (EtOH) toxicity and thiamine deficiency across the sexes using rodent models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male and female Sprague Dawley rats were assigned to chronic forced EtOH treatment (CET), pyrithiamine\u2010induced thiamine deficiency (PTD), combined CET\u2010PTD, or pair\u2010fed (PF) control treatment conditions. Following treatments, spatial working memory was assessed during a spontaneous alternation task while measuring acetylcholine (ACh) in the prefrontal cortex (PFC) and the hippocampus (HPC). The animals also underwent an operant\u2010based attentional set\u2010shifting task (ASST) for the analysis of behavioral flexibility.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Female and male rats did not differ in terms of EtOH consumption; however, the CET and CET\u2010PTD\u2010treated female rats had lower BECs than male rats. Compared with the PF group, the CET, PTD, and CET\u2010PTD groups exhibited spatial working memory impairments with corresponding reductions in ACh efflux in the PFC and HPC. The ASST revealed that CET\u2010PTD\u2010treated males and females displayed impairments marked by increased latency to make decisions. Thalamic shrinkage was prominent only in the CET\u2010PTD and PTD treatment conditions, but no sex\u2010specific effects were observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Although the CET and CET\u2010PTD\u2010treated females had lower BECs than the males, they demonstrated similar cognitive impairments. These results provide evidence that female rats experience behavioral and neurochemical disruptions at lower levels of alcohol exposure than males and that chronic EtOH and thiamine deficiencies produce a unique behavioral profile.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14594","type":"journal-article","created":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T18:26:36Z","timestamp":1615314396000},"page":"1013-1027","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Sex differences in cholinergic circuits and behavioral disruptions following chronic ethanol exposure with and without thiamine deficiency"],"prefix":"10.1111","volume":"45","author":[{"given":"Brian T.","family":"Kipp","sequence":"first","affiliation":[{"name":"Department of Psychology Binghamton University of the State University of New York New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polliana 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