Abstract
Injections of adrenocorticotropic hormone (ACTH) into the periaqueductal gray matter of drug-naive rats resulted in a dose-dependent opiate abstinence syndrome characterized by fearful hyperreactivity and explosive motor behavior. Injecting shorter chains of ACTH caused attenuated forms of this behavior. Injections of beta-endorphin at this same site caused opposite behavior: sedative, analgestic, and catatonic. If the effects of morphine are mediated by two classes of receptor) and the other which is not stereospecific and naloxone-insensitive--the endogtor)--and the other which is not stereospecific and naloxone-insensitive the endogenous ligand of the second receptor may be ACTH. The neuropeptides ACTH and endorphin may be part of an integrated neuromodulatory system, and the opiate abstinence syndrome may be the result of an altered interaction between the two receptor systems.