In humans, heroin dependent individuals use heroin also to escape the negative affective and emotional states associated with drug withdrawal [9]. Rats self-administer beta-endorphin into the brain, supporting a role for central beta-endorphin in reinforcement [40]. There is also evidence in animals that the motivational properties of opiates are altered by spontaneous and naloxone-precipitated withdrawal [41, 42, 43]. It is reasonable, therefore, to postulate that the decreased POMC gene expression with concomitant decreases in beta-endorphin peptide biosynthesis and/or release may initiate and/or maintain behaviors leading to opiate seeking, in order to reach normal endogenous opioid tone.
