Endogenous opioid system in addiction and addiction-related behaviors

- Alterations in endogenous opioid system components occur in development of addiction.
- Human studies and animal models show opioid genes contribute to addiction risk.
- Novel molecular neuronal manipulation tools are elucidating addiction neurocircuitry.
- New pharmacological targets/pathways hold promise for novel addiction therapeutics.

Since the discovery and verification of the components of the endogenous opioid system in the 1970s, consisting of the mu, kappa, and delta-opioid receptors, and the cognate ligands β-endorphin, the enkephalins, and the dynorphins, a role for the endogenous opioid system in addiction to opiates has been established. Further, studies demonstrated that long term opiate addiction results in a relative endogenous endorphin deficiency which contributes to the chronic relapsing nature of the disease. Subsequent studies, utilizing pharmacological approaches, gene expression and receptor binding techniques in animal models of addiction, as well as transgenic mouse knockout studies, have revealed the endogenous opioid system to be important in the effects of other addictive substances, and this has been verified in human genetics studies demonstrating associations of variants in genes encoding the components of the opioid system with addiction to opiates, cocaine, and alcohol.