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

Abstract

Adolescent cocaine exposure (ACE) increases the risk of suffering psychiatric disorders including anxiety in later life, which is a big public health concern with limited treating options. Consistent with our previous study, we found that ACE mice exhibited obvious anxiety-like behaviors in their adulthood, which was efficiently suppressed by electro-acupuncture (EA) at acupoints of Baihui (GV 20) and Yintang (GV 29) with stimulus of a mixed frequency of 2/100 Hz for 28 withdrawal days. In the claustrum (CL) of ACE mice, more CaMKII-positive neurons (CaMKIICL) were activated, accompanied with increased expression of dopamine receptor 1 (D1R) on them (D1RCaMKII) and phosphorylated-EKR (p-ERK), p-CREB, and BDNF protein levels. Local blockade of CL D1R by SCH23390 or specific knockdown of CL D1RCaMKII by virus suppressed both anxiety-like behaviors and CaMKIICL activity in ACE mice of adulthood, indicating the critical role of CL D1RCaMKII in ACE-enhanced anxiety. Importantly, EA treatment suppressed CaMKIICL activity and D1RCaMKII staining, along with attenuated levels of p-CREB and BDNF in CL of ACE mice. Collectively, our study for the first time identified a novel molecular mechanism of CL D1RCaMKII and CaMKIICL activity in the process of ACE-increased anxiety in adulthood. Further, by targeting CL D1RCaMKII, EA at acupoints of GV 20 and GV 29 serves as preventative strategy to adolescent drugs exposure-induced anxiety in the later life.