AbstractThe purpose of this study was to compare the effects of amphetamine exposure on subsequent amphetamine‐induced changes in behavior and dopamine (DA) release in the dorsal and ventral striatum, as a function of time following the discontinuation of repeated amphetamine treatment. Rats were pretreated with either saline or an escalating‐dose amphetamine regimen, and then received a 0.5 mg/kg amphetamine “challenge” after either 3, 7, or 28 days of withdrawal. Animals tested after 28 days of withdrawal were hypersensitive (sensitized) to the locomotor‐activating effects of amphetamine, and relative to control animals showed a significant enhancement in amphetamine‐stimulated DA release in both the dorsal and ventral striatum, as revealed by in vivo microdialysis. Animals tested after only 3 or 7 days of withdrawal showed neither behavioral sensitization nor enhanced amphetamine‐stimulated DA release. These results establish that time‐dependent changes in behavioral sensitization to amphetamine are associated with time‐dependent changes in amphetamine‐stimulated DA release, and support the hypothesis that persistent sensitization‐related changes in striatal DA neurotransmission contribute to the expression of behavioral sensitization.