Blockade by reserpine of methylphenidate-induced release of brain dopamine.

The cerebroventricular systems of cats were perfused by introducing artificial cerebrospinal fluid into a lateral ventricle and collecting the perfusate at the aqueduct. 3-H-tyrosine was continuously added to the perfusing cerebrospinal fluid and the perfusate was analyzed for 3-H-catecholamines. Intraventricular or intravenous administration of methylphenidate increased the efflux of 3-H-dopamine. In cats pretreated with reserpine, this response to methylphenidate was reduced while the efflux of 3-H-dopamine caused by delta-amphetamine was slightly increased. These results provide direct biochemical evidence in support of the hypothesis that the central stimulant action of amphetamine and methylphenidate result from their abilities to preferentially release dopamine from "newly synthesized" and "stored" pools, respectively.