title: Long-term protective effects of methamphetamine preconditioning against single-day methamphetamine toxic challenges.
abstract: Methamphetamine (METH) use is associated with neurotoxic effects which include decreased levels of dopamine (DA), serotonin (5-HT) and their metabolites in the brain. We have shown that escalating METH dosing can protect against METH induced neurotoxicity in rats sacrificed within 24 hours after a toxic METH challenge. The purpose of the current study was to investigate if the protective effects of METH persisted for a long period of time. We also tested if a second challenge with a toxic dose of METH would cause further damage to monoaminergic terminals. Saline-pretreated rats showed significant METH-induced decreases in striatal DA and 5-HT levels in rats sacrificed 2 weeks after the challenge. Rats that received two METH challenges showed no further decreases in striatal DA or 5-HT levels in comparison to the single METH challenge. In contrast, METH-pretreated rats showed significant protection against METH-induced striatal DA and 5-HT depletion. In addition, the METH challenge causes substantial decreases in cortical 5-HT levels which were not further potentiated by a second drug challenge. METH preconditioning provided almost complete protection against METH -induced 5-HT depletion. These results are consistent with the idea that METH pretreatment renders the brain refractory to METH-induced degeneration of brain monoaminergic systems.
authors: Molecular Neuropsychiatry Research Branch, Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD 21224, USA.
authors: A B
authors: AB
authors: Hodges
authors: B
authors: B
authors: Ladenheim
authors: M T
authors: MT
authors: McCoy
authors: G
authors: G
authors: Beauvais
authors: N
authors: N
authors: Cai
authors: I N
authors: IN
authors: Krasnova
authors: J L
authors: JL
authors: Cadet