Differential effects of D- and L-amphetamine and methylphenidate on rat striatal dopamine biosynthesis

Methylphenidate and the optical isomers of amphetamine have differential effects, in vivo and in vitro on rat striatal synaptosomal dopamine (DA) biosynthesis. Whereas the systemic administration of D- or L-amphetamine produces a dose-dependent decrease in synaptosomal DA synthesis, with ED₅₀'s of 1.1 and 3.5 mg/kg, respectively, methylphenidate, at doses which produce comparable degrees of stereotyped behavior, has no effect on this measure of DA biosynthesis. In vitro, D- and L-amphetamine exhibit a three-fold difference in ED₅₀'s (1 × 10⁻⁶ M and 3 × 10⁻⁶ M, respectively) with respect to both activation of striatal synaptosomal DA synthesis, and to reversal of reserpine-induced inhibition of DA synthesis. In contrast, although in vitro methylphenidate can partially activate DA synthesis, it does not overcome the reserpine-induced inhibition. The data are discussed in terms of the possible differential mechanisms by which these two types of stimulants may exert their effects on stereotypy.