Mu-opioid receptors (MOPRs) are the target of heroin and other prescription opioids, which is the underlying neurobiology responsible for endemic addiction morbidity and mortality in the US.

Opioids in the Brain

The opioid system consists of three receptors, mu, delta, and kappa. Opioid receptors are activated in response to natural rewarding stimuli and by drugs of abuse, which causes neuroadaptation to the opioidergic reward system as addiction develops. Charbogne and colleagues (Journal of Biopsychiatry, 2016) report that Naloxone is reversible, Mu opioid receptors (MORs) mediate analgesic, euphorigenic, and other biological effects of opioids. Yet the aberrant activation and modifications of the mu opioid system associated with drug craving and relapse are not well understood.

Behavioral analysis of OPRM1 mice shows that this population does regulate locomotor and motivational effects of heroin. These receptors do not contribute to heroin-positive reinforcement. Beyond a well-established role in reward processing at the level of local ventral tegmental area neurons, MORs moderate motivation for appetitive stimuli and motivation to obtain heroin and food reward, revealing a yet unreported role for MORs within addiction circuits. Several brain areas responsible for MOR-mediated reward have been identified. Yet more research is needed to establish the key underlying molecular function of the system and to locate neural sites where opioid peptides and receptors contribute to the onset of addictive disease.

Why Does This Matter?

We wonder why do some people exposed to prescription opioids become addicts quickly, others slowly, while others do not. We also have wondered about individual differences in opioid medication response, toxicity, addiction, and relapse. Genetic association studies reveal that the OPRM1 A118G genotype (found in up to 30% of Caucasian and 60% of Asian populations) increases the risk of heroin addiction. Accordingly, more genetic research is needed to further elucidate our understanding of the biology of addiction and for the development of therapeutic interventions to treat the disorder.