JWA regulates chronic morphine dependence via the delta opioid receptor

► Increased JWA expression in opioids neurocircuit regions is required for development of morphine dependence in rats. ► Knockdown JWA expression significantly reduces chronic morphine withdrawal response in rats. ► JWA interacts with DOR and maintains DOR stability via ubiquitin-proteasome pathway. ► Knockdown JWA expression inhibits morphine induced activation of MAP kinase and DARPP-32.