Laboratory of Molecular Basis of Behavior, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland.
Experimental Psychopathology Lab, Institute of Psychology of Polish Academy of Sciences, Warsaw, Poland.
Neuropsychopharmacology. 2023 Feb;48(3):436-447. doi: 10.1038/s41386-022-01464-5. Epub 2022 Oct 1.
Both human and animal studies indicate that the dentate gyrus (DG) of the hippocampus is highly exploited by drug and alcohol abuse. Yet, it is poorly understood how DG dysfunction affects addiction-related behaviors. Here, we used an animal model of alcohol use disorder (AUD) in automated IntelliCages and performed local genetic manipulation to investigate how synaptic transmission in the dorsal DG (dDG) affects alcohol-related behaviors. We show that a cue light induces potentiation-like plasticity of dDG synapses in alcohol-naive mice. This process is impaired in mice trained to drink alcohol. Acamprosate (ACA), a drug that reduces alcohol relapse, rescues the impairment of dDG synaptic transmission in alcohol mice. A molecular manipulation that reduces dDG synaptic AMPAR and NMDAR levels increases impulsive alcohol seeking during cue relapse (CR) in alcohol mice but does not affect alcohol reward, motivation or craving. These findings suggest that hindered dDG synaptic transmission specifically underlies impulsive alcohol seeking induced by alcohol cues, a core symptom of AUD.
人类和动物研究都表明，海马齿状回（DG）被滥用药物和酒精大量开发。然而，人们对 DG 功能障碍如何影响与成瘾相关的行为知之甚少。在这里，我们使用自动化 IntelliCages 中的酒精使用障碍（AUD）动物模型，并进行局部遗传操作，以研究背侧 DG（dDG）中的突触传递如何影响酒精相关行为。我们发现，在酒精-naive 小鼠中，提示光会诱导 dDG 突触产生类似于增强的可塑性。在接受饮酒训练的小鼠中，该过程受损。降低酒精复发的药物安非他酮（ACA）可挽救酒精小鼠中 dDG 突触传递的损伤。降低 dDG 突触 AMPAR 和 NMDAR 水平的分子操作会增加酒精线索复吸（CR）期间酒精小鼠的冲动性酒精寻求，但不会影响酒精奖励、动机或渴望。这些发现表明，dDG 突触传递的受阻是由酒精线索引起的冲动性酒精寻求的核心症状，这是 AUD 的一个核心症状。
