Endorphin-locus coeruleus connection mediates opiate action and withdrawal.

Endorphins and exogenous opiates inhibit the activity of the noradrenergic nucleus locus coeruleus (LC). This discovery of endorphin transmitters and their interaction with the LC has supported our studies which have suggested that the majority of the signs and symptoms of opiate withdrawal are mimicked by electrical or chemical activation of the LC. We hypothesize that this endorphin-LC connection is critical to opiate action and the withdrawal syndrome. This hypothesis suggests that chronic opiate administration inhibits LC activity and that opiate abstinence after addiction results in a release from inhibition with resultant LC hyperactivity. This hypothesis is supported by recent data suggesting that clonidine as a drug which inhibits the LC and LC-mediated noradrenergic activation, is an efficacious non-opiate treatment for opiate withdrawal. This hypothesis can be tested in man by evaluating drugs which inhibit the LC and LC-mediated behaviors for anti-withdrawal efficacy.