Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China; Institute for Brain Research, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China; Key Laboratory of Neurological Diseases, Ministry of Education, Wuhan, Hubei, P.R. China.
Cell Rep. 2024 Jul 23;43(7):114383. doi: 10.1016/j.celrep.2024.114383. Epub 2024 Jun 24.
Alcohol is the most widely used addictive substance, potentially leading to brain damage and genetic abnormalities. Despite its prevalence and associated risks, current treatments have yet to identify effective methods for reducing cravings and preventing relapse. In this study, we find that 4-Hz alternating bilateral sensory stimulation (ABS) effectively reduces ethanol-induced conditioned place preference (CPP) in male mice, while 4-Hz flash light does not exhibit therapeutic effects. Whole-brain c-Fos mapping demonstrates that 4-Hz ABS triggers notable activation in superior colliculus GABAergic neurons (SC). SC forms monosynaptic connections with ventral tegmental area dopaminergic neurons (VTA), which is implicated in ethanol-induced CPP. Bidirectional chemogenetic manipulation of SC-VTA circuit either replicates or blocks the therapeutic effects of 4-Hz ABS on ethanol-induced CPP. These findings elucidate the role of SC-VTA circuit for alleviating ethanol-related CPP by 4-Hz ABS and point to a non-drug and non-invasive approach that might have potential for treating alcohol use disorder.
酒精是最广泛使用的成瘾物质，可能导致大脑损伤和遗传异常。尽管它很普遍，且存在相关风险，但目前的治疗方法尚未确定有效减少渴望和预防复发的方法。在这项研究中，我们发现 4-Hz 交替双侧感觉刺激（ABS）可有效减少雄性小鼠的乙醇诱导的条件性位置偏好（CPP），而 4-Hz 闪烁光则没有治疗效果。全脑 c-Fos 图谱表明，4-Hz ABS 可引起上丘 GABA 能神经元（SC）的显著激活。SC 与腹侧被盖区多巴胺能神经元（VTA）形成单突触连接，这与乙醇诱导的 CPP 有关。SC-VTA 回路的双向化学遗传操作可复制或阻断 4-Hz ABS 对乙醇诱导的 CPP 的治疗作用。这些发现阐明了 SC-VTA 回路在通过 4-Hz ABS 缓解与乙醇相关的 CPP 中的作用，并指出了一种非药物和非侵入性的方法，可能有潜力治疗酒精使用障碍。
