Analgesia induced by electroconvulsive shock: brain enkephalins may mediate tolerance but not the induction of analgesia.

Electroconvulsive shock (ECS) administered to rats produces potent analgesia. This analgesic effect displays opiate characteristics with tolerance to ECS analgesia seen with repeated induction and cross tolerance observed following the chronic administration of analgesic dose of morphine. Furthermore, tolerance development after repeated ECS application could be blocked by daily pretreatment with the long acting opiate antagonist naltrexone (5 mg/kg). In contrast to these opiate characteristics of ECS analgesia, naltrexone administration (0.5, 5 and 10 mg/kg) failed to attenuate the acute analgesic effect of ECS. Measurement of brain enkephalin levels revealed an increase in enkephalin contents after 10 daily ECS applications, an effect which was not affected by naltrexone pretreatment. Acute administration of ECS did not affect brain enkephalin levels either immediately or 24 h after ECS administration. Significant increases in brain enkephalin following chronic ECS were observed in the hypothalamus and striatum but not in the mesencephalon or hindbrain. A gradual return of enkephalin levels to baseline values was seen with days when ECS was no longer administered. Parallel behavioral studies showed that ECS analgesia also showed a gradual recovery from tolerance after discontinuation of chronic ECS. Based on these and previous studies we propose that different systems may mediate the acute analgesic effect of ECS on the one hand, and the tolerance to such an effect observed after repeated administration on the other. We further suggest that the acute action of ECS may be mediated by substances with only partial opiate characteristics, while the long term effects observed may be due to the increase in brain enkephalin contents after chronic ECS application.