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.
Kantor
Lana
L
Department of Pharmacology, University of Michigan School of Medicine, 2220 MSRB III, 1150 W Medical Center Dr, Ann Arbor, MI 48109-0632, USA.
Park
Yang Hae
YH
Wang
Kevin K W
KK
Gnegy
Margaret
M
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D005473:Fluoxetine / Q000031:analogs & derivatives* / Q000378:metabolism; D020932:Nerve Growth Factor / Q000187:drug effects; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats
D005473:Fluoxetine; C011386:nisoxetine; D020932:Nerve Growth Factor; D000661:Amphetamine; D004298:Dopamine