Thalamostriatal circuit as a therapeutic target of alcohol use disorder

Alcohol Use Disorder (AUD) is a chronic neuropsychiatric disorder characterized by high relapse rates and limited treatment efficacy. In this review, we focus on evidence that chronic alcohol exposure disrupts intralaminar thalamic input to the dorsal striatum, particularly Pf/CM-Pf-related regulation of dorsomedial striatal cholinergic interneurons, a pathway implicated in reversal learning and cognitive flexibility in preclinical models. We further distinguish this circuit from PVT-centered thalamic pathways that influence alcohol-related reward, aversion, and relapse-like behavior through ventral striatal and extended-amygdala networks. We summarize human imaging and behavioral findings that are broadly consistent with altered thalamic-striatal-frontal network function in AUD, while emphasizing that these data remain largely correlational. Finally, we review invasive and emerging noninvasive neuromodulation strategies and argue that thalamic circuit targeting should be considered a mechanistically motivated but as yet unvalidated therapeutic direction in AUD.