Attenuation of morphine tolerance development by electroconvulsive shock in mice

The development of tolerance to morphine has been proposed as being analogous to learning or memory, since the presentation of a novel stimulus (morphine) to an organism results in an altered response on subsequent presentations of the same stimulus. Electroconvulsive shock has been widely used to disrupt memory in animals and its effect on the development of tolerance to morphine was examined. Pretreatment of mice with six, progressively increasing intraperitoneal doses of morphine induced tolerance to an excitant action of morphine, shown by a marked reduction in the locomotor activity elicited by a subsequent intraperitoneal test dose of morphine. In three separate experiments, the administration of eleetroconvulsive shock 2–3 hr after each pretreatment with morphine attenuated the degree of tolerance developed. The eleetroconvulsive shock had no significant effect on the locomotor activity of non-tolerant mice tested under similar conditions in each experiment. In a single pilot study, electroconvulsive shock was found to reduce the frequency of jumping precipitated by an intraperitoneal dose of naloxone, suggesting a possible decrease in the degree of dependence. The present results are interpreted as supporting the view that the mechanisms of morphine tolerance may be similar to those involved in learning or memory.