A “challenge” METH regimen decreases both (A) the velocity and magnitude of K+-stimulated DA release from striatal suspensions and (B) DA content in the VMAT-2M- and VMAT-2C-associated vesicle fractions (B). Rats received four injections of METH (7.5 mg/kg/injection, s.c., 2-h intervals) or saline vehicle (1 ml/kg/injection, s.c., 2-h intervals) and were killed 1 h later. Columns represent the mean ± 1 S.E.M. of 6 to 8 independent determinations. *, indicates a statistical difference between saline- and METH-treated animals.