Department of Psychological Sciences, Purdue University, West Lafayette, IN, 47907, USA; Center for Research on Brain, Behavior, and NeuroRehabilitation (CEREBBRAL), Purdue University, West Lafayette, IN, 47907, USA.
School of Health Sciences, Purdue University, West Lafayette, IN, 47907, USA; Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN, 47907, USA.
Food Chem Toxicol. 2023 Apr;174:113685. doi: 10.1016/j.fct.2023.113685. Epub 2023 Feb 20.
Parkinson's Disease (PD) and Alcohol Use Disorder (AUD) are disorders that involve similar dopaminergic neurobiological pathways and dysregulations in motivation- and reward-related behaviors. This study explored whether exposure to a PD-related neurotoxicant, paraquat (PQ), alters binge-like alcohol drinking and striatal monoamines in mice selectively bred for high alcohol preference (HAP), and whether these effects are sex-dependent. Previous studies found female mice are less susceptible to PD-related toxicants compared to male mice. Mice were treated with PQ or vehicle over 3 weeks (10 mg/kg, i.p. once per week) and binge-like alcohol [20% (v/v)] drinking was assessed. Mice were euthanized and brains were microdissected for monoamine analyses by high performance liquid chromatography with electrochemical detection (HPLC-ECD). PQ-treated HAP male mice showed significantly decreased binge-like alcohol drinking and ventral striatal 3,4-Dihydroxyphenylacetic acid (DOPAC) levels compared to vehicle-treated HAP mice. These effects were absent in female HAP mice. These findings suggest that male HAP mice may be more susceptible than female mice to PQ's disruptive effects on binge-like alcohol drinking and associated monoamine neurochemistry and may be relevant for understanding neurodegenerative processes implicated in PD and AUD.
帕金森病（PD）和酒精使用障碍（AUD）是涉及相似多巴胺能神经生物学途径和动机及奖励相关行为失调的疾病。本研究探讨了暴露于与 PD 相关的神经毒素百草枯（PQ）是否会改变高酒精偏好（HAP）选择性繁殖的小鼠的 binge-like 饮酒和纹状体单胺，以及这些影响是否具有性别依赖性。先前的研究发现，与雄性小鼠相比，雌性小鼠对 PD 相关毒素的敏感性较低。小鼠接受 PQ 或载体处理 3 周（10mg/kg，每周腹腔注射一次），并评估 binge-like 酒精[20%（v/v）]的摄入。安乐死后，通过高效液相色谱电化学检测（HPLC-ECD）对大脑进行单胺分析的微透析。与 vehicle 处理的 HAP 小鼠相比，PQ 处理的 HAP 雄性小鼠的 binge-like 酒精摄入和腹侧纹状体 3,4-二羟苯乙酸（DOPAC）水平明显降低。这些影响在雌性 HAP 小鼠中不存在。这些发现表明，雄性 HAP 小鼠可能比雌性小鼠更容易受到 PQ 对 binge-like 酒精摄入及相关单胺神经化学的破坏作用的影响，这可能与理解 PD 和 AUD 中涉及的神经退行性过程有关。
