Differential effects of D- and L-amphetamine on behavior and on catecholamine disposition in dopamine and norepinephrine containing neurons of rat brain

We have compared the effects of D- and L-amphetamine on the disposition of intraventricularly administered [³H]norepinephrine and [³H]dopamine and on endogenous catecholamine in various regions of the rat brain. In behavioral experiments the effects of D- and L-amphetamine on locomotor activity and on compulsive gnawing behavior were also compared. In brain areas where norepinephrine is the predominant catecholamine, D-amphetamine but not its L-isomer inhibited [³H]catecholamine accumulation and lowered endogenous norepinephrine levels. In the corpus striatum, a dopaminergic brain region, both D- and L-amphetamine markedly reduced accumulation of [³H]catecholamines. D-Amphetamine was 10 times as potent as L-amphetamine in enhancing locomotor activity, but was only twice as active in evoking compulsive gnawing behavior. Our results suggest that brain norepinephrine is selectively involved in mediating amphetamine-induced locomotor stimulation while a dopaminergic component may participate in eliciting the compulsive gnawing syndrome.