title: Repeated, intermittent treatment with amphetamine induces neurite outgrowth in rat pheochromocytoma cells (PC12 cells).
abstract: Repeated, intermittent treatment with amphetamine (AMPH) leads to long-term neurobiological adaptations in rat brain including an increased number and branching of dendritic spines. This effect depends upon several different cell types in the intact brain. Here we demonstrate that repeated, intermittent AMPH treatment induces neurite outgrowth in cultured PC12 cells without the requirement for integrated synaptic pathways. PC12 cells were treated with 1 micro M AMPH for 5 min a day, for 5 days. After 10 days of withdrawal, there was an increase in the percentage of cells with neurites ( approximately 30%) and the length of neurites as well as an increase in the level of GAP-43 and neurofilament-M. Neurite outgrowth was enhanced as withdrawal time was increased. Neurite outgrowth was much greater following repeated, intermittent treatment with AMPH compared to continuous or single treatment with AMPH. Pretreatment with cocaine, a monoamine transporter blocker, inhibited the AMPH-mediated increase in neurite outgrowth. Neither NGF antibody nor DA receptor antagonists blocked AMPH-induced neurite outgrowth, demonstrating that AMPH-induced neurite outgrowth is not dependent on endogenous NGF release or DA receptors. Thus we have demonstrated that repeated, intermittent treatment with AMPH has a neurotrophic effect in PC12 cells. The effect requires the action of AMPH on the norepinephrine transporter, and shares characteristics in its development with other forms of sensitization but does not require an intact neuroanatomy.
authors.affiliation: Department of Pharmacology, 2220 MSRB III, University of Michigan School of Medicine, 1150 W Medical Center Dr, Ann Arbor, MI 48109-0632, USA.
authors.forename: Yang Hae
authors.initials: YH
authors.lastname: Park
authors.forename: Lana
authors.initials: L
authors.lastname: Kantor
authors.forename: Kevin K W
authors.initials: KK
authors.lastname: Wang
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Gnegy
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology; D000661:Amphetamine / Q000494:pharmacology*; D019969:Amphetamine-Related Disorders / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development*; D003042:Cocaine / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004334:Drug Administration Schedule; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins; D016716:PC12 Cells; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D027981:Symporters / Q000187:drug effects / Q000378:metabolism
chemical_list: D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D009414:Nerve Growth Factors; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011954:Receptors, Dopamine; C493226:Slc6a2 protein, rat; D027981:Symporters; D020932:Nerve Growth Factor; D000661:Amphetamine; D003042:Cocaine; D009638:Norepinephrine