Dopamine receptor 1 on CaMKII-positive neurons within claustrum mediates adolescent cocaine exposure-induced anxiety and electro-acupuncture therapy

Abstract

AbstractAdolescent cocaine exposure (ACE) increases risk of developing psychiatric problems such as anxiety, which may drive relapse in later life, however, its underlying molecular mechanism remains poorly understood.MethodsACE male mice model were established by exposing to cocaine during adolescent period. Elevated plus maze (EPM) were used to assess anxiety-like behaviors in mice. Within claustrum, local injection of SCH-23390, a specific antagonist for dopamine receptor 1 (D1R), or D1R knocking-down virus were used to regulate D1R function or expression on CaMKII-positive neurons (D1RCaMKII)in vivo. Electro-acupuncture (EA) treatment was performed at acupoints of Baihui and Yintang during withdrawal period.ResultsWe found that ACE mice exhibited anxiety-like behaviors, along with more activated CaMKII-positive neurons and increased D1RCaMKIIlevels in claustrum during adulthood. Locally inhibiting D1R function or knocking-down D1RCaMKIIlevels in claustrum efficiently reduced claustrum activation, and ultimately suppressed anxiety in ACE mice during adulthood. EA treatment alleviated ACE-evoked claustrum activation and anxiety by suppressing claustral D1RCaMKII.ConclusionOur findings identified a novel role of claustrum in ACE-induced anxiety, and put new insight into the claustral D1RCaMKII. The claustral D1RCaMKIImight be a promising pharmacological target, such as EA treatment, to treat drugs-related psychiatric disorders.Graphic abstract