AMPHETAMINE RELEASES DOPAMINE FROM SYNAPTIC VESICLES BY DUAL MECHANISMS

Low concentrations of D-amphetamine (AMPH) released [H-3]dopamine (DA) from purified, rat brain synaptic vesicles with exponential kinetics and a half-time of 4 min. Slight alkalinization of the vesicles by AMP H seemed unable to account for this release. instead, it is likely tha t AMPH partially inhibits DA uptake after which DA escapes by an uptak e-independent pathway. At high concentrations the proton gradient was severely reduced by AMPH and DA was released with a half-time of <1 mi n. Loss of the proton gradient was sufficient to account for this DA r elease. These results show that low concentrations of AMPH release DA from synaptic vesicles and suggest that release occurs by different me chanisms at low and high AMPH concentrations.