A neuronal basis for the alerting action of (+)-amphetamine.

1. (+)-Amphetamine mimicked the excitatory and inhibitory actions of (-)-noradrenaline on single neurones in the brain stem of acute halothaneanaesthetized rats when these compounds were applied by iontophoresis. (+)-Amphetamine had no actions on neurones unaffected by (-)-noradrenaline.2. These mimicking actions of (+)-amphetamine could not be observed 20 h after treatment of the animals with reserpine 5 mg/kg.3. The enzyme inhibitors alpha-methyl-p-tyrosine and FLA 63 also greatly reduced the number of (-)-noradrenaline-mimicking responses to (+)-amphetamine.4. In animals pretreated with alpha-methyl-p-tyrosine, but not in those pretreated with FLA 63, excitatory actions of (+)-amphetamine on neurones excited by (-)-noradrenaline could be elicited 45-90 min after systemic injection of L-DOPA.5. These results indicate that (+)-amphetamine can release noradrenaline from presynaptic sites in the brain stem, which may be a basis for its alerting actions.