Behavioral and neurochemical interactions of dextroamphetamine and methylphenidate in rats.

The effects of dextroamphetamine and methylphenidate on locomotor activity and brain levels of norepinephrine and dopamine were compared in male Sprague-Dawley rats. Both drugs produced a dose-related increase in locomotor activity during the hour immediately following intraperitoneal administration. However, combined administration of drugs elicited only the effect of dextroamphetamine. Brain levels of norepinephrine and dopamine also increased 1 hr after dextroamphetamine dosing. Methylphenidate did not exhibit these effects and antagonized the neurochemical changes produced by dextroamphetamine. Although both drugs are considered to exert their effects by indirect activation of brain catecholamine systems, differences in their mechanism of action appear to result in a lack of additive or antagonistic effects when dextroamphetamine and methylphenidate are coadministered. These findings may have clinical significance with respect to the use of such agents in minimal brain dysfunction.