Opiate dependence and withdrawal--a new synthesis?

There is a growing body of evidence to suggest that adrenocorticotropin (ACTH) may have a physiological role as an endogenous contra-opioid agonist. In addition to having appreciable affinity for opiate receptors and inducing many behavioural and intracellular effects opposite to those observed following opioid administration, ACTH may interact with endorphins in a mutually antagonistic manner. On the basis of these data a model of opiate dependence is proposed whereby several aspects of the opiate abstinence syndrome may be attributed to the excitatory actions of ACTH acting at opiate receptors. Thus, it may be predicted that opiate antagonist administration during primary abstinence should significantly attenuate many aspects of this behavioural syndrome. The present study was conducted in order to investigate this hypothesis. Results indicated that whilst naloxone (1.5 mg/kg) exerted little influence in non-dependent animals, it significantly attenuated abstinence-exacerbated grooming, body shaking, teeth chattering and sneezing, in addition to completely antagonizing withdrawal hyperalgesia in post-dependent animals. These data are consistent with the proposed existence of an endogenous contra-opioid ligand, the antagonism of which markedly reduces the severity of the morphine withdrawal syndrome.