The G protein-coupled mu opioid receptor (encoded by the OPRM1 gene) is the major site of action for endogenous opioids, opiate and opioid analgesic drugs, and exogenous opioid drugs such as methadone, heroin and morphine (Kreek 2005). The receptor mediates the action of non-opioid drugs of abuse (e.g. alcohol, nicotine) and the stress-responsive HPA axis. Receptor activation results in the opening of G protein-gated inwardly-rectifying K+ (GIRK) channels, inhibition of voltage-gated Ca2+ channels, and reduction of adenylyl cyclase-mediated cAMP production. Binding of beta-endorphin results in disinhibition of dopaminergic neurons and this dopamine influx has been associated with reward and reinforcement and is believed to contribute to the development of drug dependence.
