In rats, morphine withdrawal was shown to increase oprm1 expression in the hypothalamus and striatum (Zhou et al, 2006). Acute and subacute cocaine administration increases oprm1 expression in specific brain regions (Azaryan et al, 1998; Yuferov et al, 1999). Also, chronic binge cocaine administration was reported to increase μ-opioid receptor density in specific brain regions (Unterwald et al, 1994), and steady-state methadone administration was shown to prevent cocaine-induced conditioned place preference and to attenuate the increase of OPRM1 mRNA in the nucleus accumbens during cocaine withdrawal (Leri et al, 2006). Further, in rats, the increase in μ-opioid receptor density is reported to persist for over two weeks following cessation of cocaine administration (Bailey et al, 2005), and in humans, μ-opioid receptor binding potential is increased compared to controls during cocaine abstinence (Gorelick et al, 2005). These effects may explain the efficacy of methadone maintenance treatment for cocaine addiction as well as for heroin addiction (Peles et al, 2006). A possible mechanism of methadone pharmacotherapy is to down-regulate the increased OPRM1 expression during heroin withdrawal, thus contributing to the reestablishment of normal μ-opioid receptor levels.
