Amnesia as a major side effect of electroconvulsive shock: the possible involvement of hypothalamic opioid systems

Electroconvulsive shock (ECS) is used in the treatment of depression and causes antero- and retrograde amnesia as a side effect. One of the many neurochemical effects of ECS is depletion of brain beta-endorphin and Met-enkephalin. These two opioid peptides cause antero- and retrograde amnesia also. Naloxone antagonizes the amnestic effect of ECS and of the opioid peptides. Thus, it is possible that the amnestic effect of ECS is mediated by an endogenous release of the peptides. Surgical posterior hypothalamic deafferentation, but not anterior deafferentation or fornix transection, abolishes the amnestic effect of ECS. This suggests that the hyperactivation of endogenous opioid systems by ECS that leads to amnesia is mediated by posterior ascending fibers to the hypothalamus. The relevance of these considerations to the treatment of depression merits investigation.