Magnesium ions prevent the development of hyperkinesia evoked by administration of picrotoxin into the rat neostriatum.

Chronic experiments on rats were performed to study the effects of daily administration of the GABA(A) receptor antagonist picrotoxin (2 microg) into the rostral neostriatum in rats. Picrotoxin was injected in 1 microl of sterile apyrogenic physiological saline or in 1 microl of 1.0 M or 1.5 M MgCl(2); control animals received physiological saline or 1.0 M MgCl(2). Picrotoxin given in physiological saline induced impairments in conditioned reflex (avoidance) and free motor behavior and produced clear stereotypical imperative movements in the form of choreomyoclonic hyperkinesia of the paws, head, and trunk. These motor impairments resembled the manifestaitons of basal ganglia dysfunction typical of Huntingdon's chorea in humans. Magnesium ions prevented both the development of hyperkinesia and impairments of learned behavior. Given that magnesium is a nonspecific calcium channel antagonist, it can be suggested that one of the leading mechanisms of development of hyperkinesias is impairment of calcium homeostasis in striatal neurons.