Department of Psychology, Binghamton University of the State University of New York, New York, NY, USA.
Alcohol Clin Exp Res. 2021 May;45(5):1013-1027. doi: 10.1111/acer.14594. Epub 2021 Apr 3.
Few studies have investigated differences in the vulnerabilities of males and females to alcohol use disorder and alcohol-related brain damage (ARBD). 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.
Male and female Sprague Dawley rats were assigned to chronic forced EtOH treatment (CET), pyrithiamine-induced thiamine deficiency (PTD), combined CET-PTD, or pair-fed (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-based attentional set-shifting task (ASST) for the analysis of behavioral flexibility.
Female and male rats did not differ in terms of EtOH consumption; however, the CET and CET-PTD-treated female rats had lower BECs than male rats. Compared with the PF group, the CET, PTD, and CET-PTD groups exhibited spatial working memory impairments with corresponding reductions in ACh efflux in the PFC and HPC. The ASST revealed that CET-PTD-treated males and females displayed impairments marked by increased latency to make decisions. Thalamic shrinkage was prominent only in the CET-PTD and PTD treatment conditions, but no sex-specific effects were observed.
Although the CET and CET-PTD-treated 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.
很少有研究调查男性和女性对酒精使用障碍和酒精相关脑损伤 (ARBD) 的易感性差异。根据流行病学和临床发现，女性似乎对酒精和硫胺素缺乏的影响更为敏感，并且在从神经认知缺陷中恢复方面的预后比男性更差。本研究旨在使用啮齿动物模型来描述慢性乙醇 (EtOH) 毒性和硫胺素缺乏对两性的影响。
雄性和雌性 Sprague Dawley 大鼠被分配到慢性强制 EtOH 治疗 (CET)、吡哆醇诱导的硫胺素缺乏 (PTD)、联合 CET-PTD 或配对喂养 (PF) 对照治疗条件。治疗后，通过自发交替任务评估空间工作记忆，同时测量前额叶皮层 (PFC) 和海马 (HPC) 中的乙酰胆碱 (ACh)。动物还进行了基于操作的注意定势转移任务 (ASST)，以分析行为灵活性。
雌性和雄性大鼠的 EtOH 消耗量没有差异；然而，CET 和 CET-PTD 治疗的雌性大鼠的 BEC 低于雄性大鼠。与 PF 组相比，CET、PTD 和 CET-PTD 组表现出空间工作记忆障碍，同时 PFC 和 HPC 中的 ACh 外排减少。ASST 表明，CET-PTD 治疗的雄性和雌性大鼠表现出决策时延长潜伏期的损伤。只有在 CET-PTD 和 PTD 治疗条件下才会出现丘脑萎缩，但没有观察到性别特异性影响。
尽管 CET 和 CET-PTD 治疗的雌性大鼠的 BEC 低于雄性大鼠，但它们表现出相似的认知障碍。这些结果表明，雌性大鼠在暴露于较低水平的酒精时会经历行为和神经化学紊乱，而慢性 EtOH 和硫胺素缺乏会产生独特的行为特征。
