Role of dopamine mesolimbic system in opioid action of psychotropic analgesic nitrous oxide in alcohol and drug withdrawal.

Psychotropic analgesic nitrous oxide (PAN) has been used successfully in the treatment of alcohol and drug withdrawal in > 15,000 cases. It is an opioid and thus the first gaseous member of the opioid family. We propose the existence of two mutually antagonistic opioid systems as underlying addictive withdrawal states; mu and kappa. PAN as a multipotent opioid activates these systems. Dopamine (DA) activity in the nucleus accumbens appears to be controlled by kappa- and mu-receptors, with mu enhancing and kappa inhibiting release. In morphine and alcohol withdrawal, there is severe inhibition of dopamine release from nucleus accumbens. We thus infer that a probable major therapeutic effect of PAN is in modulating this dopamine system, thereby correcting the severe deficit in dopamine release found in withdrawal states. This has been achieved without any transfer of addiction to PAN in any of the treated patients because of modulation of DA in the nucleus accumbens by PAN. This effect may also explain its anticraving action.