Differential decreases in c-fos and aldolase C mRNA expression in the rat cerebellum after repeated administration of methamphetamine.

The effects of repeated methamphetamine administration on c-fos mRNA and aldolase C (Zebrin) mRNA expression in the rat cerebellum were investigated. A single dose of methamphetamine induced c-fos mRNA expression in granule and Purkinje cells of both anterior and posterior lobes. In the posterior lobe, in particular, c-fos mRNA signals were distributed in a parasagittal organization, like Zebrin bands. Repeated methamphetamine injections reduced methamphetamine-induced c-fos mRNA signals in the anterior hemisphere and in part of the posterior vermis (lobule VII) and posterior hemisphere. Aldolase C mRNA signals in Purkinje cells decreased only in lobules where methamphetamine-induced c-fos signals were not reduced (lobules VI and IX). Therefore, differential decreases in c-fos mRNA and aldolase C mRNA expression after repeated methamphetamine administration depend upon the localization of Purkinje cells in the cerebellum. Since c-fos mRNA and aldolase C mRNA expressions are markers of excitability and the metabolic state of Purkinje cells, respectively, hypofunction of inhibitory Purkinje cells could be induced if methamphetamine is repeatedly injected. Since repeated methamphetamine administration in this experimental paradigm increased horizontal movement and the rearing activity of rats, the hemisphere of the cerebellum may be involved in development of methamphetamine-induced motor behavioral sensitization in addition to the striatum and the nucleus accumbens.