Introduction
Drug
addiction is a chronic and recurrent brain disease, which is
characterized by compulsive seeking drug and intense drug craving
(Shippenberg et al., 2007a; Zhu et al., 2015; Wu et al., 2016). Opioid
addiction is the accumulated results of tolerance and dependence, mainly
including physical dependence and psychological dependence. Physical
dependence seeks drug repeatedly and increases gradually the dose of the
drug to avoid withdrawal symptoms (Nestler et al., 1993). Psychological
dependence refers to the craving for seeking drug and euphoria achieved
by repeated medication, which is not easy to eliminate, prompting to
relapse. Drug relapse can persist a long time after the cessation of
drug use in the human (Robbins et al., 2008) and the high rate of
relapse after detoxification is a major clinical problem and becomes
severe challenge to treat drug abuse (Aguilar et al., 2009). Morphine
and related opioids are the most potent and widely used analgesics for
treating moderate to severe pain. However, the development of physical
and psychological dependence is an important limitation to use opioid
drugs in the treatment of chronic pain, leading to misappropriate use
and abuse liability (Ruzza et al., 2019). Drug addiction in western
countries particularly in the USA has become a health and social problem
in recent years that needs to be urgently addressed and is a unmet
medical need (Wingo et al., 2016; Ezard et al., 2018).