D1RCaMKII in claustrum mediates ACE-induced anxiety and electro-acupuncture therapy

Adolescent cocaine exposure (ACE) increases risk of developing psychiatric problems such as anxiety in their later life. Here, ACE animal models were established by exposing to cocaine during adolescent period in male mice, followed by electro-acupuncture (EA) at acupoints of Baihui (GV 20) and Yintang (GV 29) with stimuli of a mixed frequency of 2/100 Hz for 28 withdrawal days. ACE mice of adulthood exhibited anxiety-like behaviors, accompanying with obviously activated CaMKII-positive neurons and increased dopamine receptor 1 (D1R) on CaMKII-positive neurons (D1RCaMKII) in claustrum. In vivo, local blocking D1R with SCH23390 or knocking-down of D1RCaMKII with specific virus efficiently reduced claustrum activation, and ultimately suppressed anxiety in ACE mice of adulthood. EA treatment alleviated ACE-induced anxiety by suppressing D1RCaMKII and claustrum activation. Our findings identified a novel role of claustrum in ACE-induced anxiety, and put new insight into the function of claustral D1RCaMKII. Targeting claustral D1RCaMKII, EA obviously alleviates ACE-induced anxiety in mice of adulthood.