Enhanced amphetamine-mediated dopamine release develops in PC12 cells after repeated amphetamine treatment.

We previously demonstrated that rats treated with repeated, intermittent amphetamine displayed enhanced amphetamine-mediated dopamine release in the striatum. In this study, we examined whether amphetamine pretreatment would elicit enhanced amphetamine-mediated dopamine release in a cultured cell line in the absence of intact synaptic connections. PC12 cells pretreated with 1 microM amphetamine produced over twofold increase in amphetamine-mediated dopamine release upon challenge with 1 microM amphetamine as compared with vehicle-treated cells. No change in norepinephrine transporter density or [3H]dopamine uptake was detected. A withdrawal time of 6 days was required to observe the enhanced amphetamine-mediated dopamine release. Differentiation of the cells with nerve growth factor did not alter the amphetamine-mediated dopamine release in control cells or the development of enhanced release in amphetamine-treated cells. Our results demonstrate that repeated, intermittent amphetamine leads to a neuroadaptation resulting in enhanced amphetamine-induced dopamine release in catecholaminergic cells without the need of an intact neuroanatomy.