AKAP150 from nucleus accumbens dopamine D1 and D2 receptor-expressing medium spiny neurons regulates morphine withdrawal

Abstract

Dopamine D1 receptor-expressing medium spiny neurons (D1R-MSNs) and dopamine D2 receptor-expressing MSNs (D2R-MSNs) in nucleus accumbens (NAc) have been demonstrated to show different effects on reward and memory of abstinence. A-kinase anchoring protein 150 (AKAP150) expression in NAc is significantly upregulated and contributes to the morphine withdrawal behavior. However, the underlying mechanism of AKAP150 under opioid withdrawal remains unclear. In this study, AKAP150 expression in NAc is upregulated in naloxone-precipitated morphine withdrawal model, and knockdown of AKAP150 alleviates morphine withdrawal somatic signs and improves the performance of conditioned place aversion (CPA) test. AKAP150 in NAc D1R-MSNs is related to modulation of the performance of morphine withdrawal CPA test, while AKAP150 in NAc D2R-MSNs is relevant to the severity of somatic responses. Our results suggest that AKAP150 from D1R-MSNs or D2R-MSNs in NAc contributes to the developmental process of morphine withdrawal but plays different roles in aspects of behavior or psychology.