Running wheel exercise ameliorates methamphetamine-induced damage to dopamine and serotonin terminals
Article first published online: 3 NOV 2011
Copyright © 2011 Wiley Periodicals, Inc.
Volume 66, Issue 1, pages 71–80, January 2012
How to Cite
O'dell, S. J., Galvez, B. A., Ball, A. J. and Marshall, J. F. (2012), Running wheel exercise ameliorates methamphetamine-induced damage to dopamine and serotonin terminals. Synapse, 66: 71–80. doi: 10.1002/syn.20989
- Issue published online: 18 NOV 2011
- Article first published online: 3 NOV 2011
- Accepted manuscript online: 27 SEP 2011 07:35PM EST
- Manuscript Accepted: 14 SEP 2011
- Manuscript Received: 19 AUG 2011
- PHS. Grant Number: RO1-DA012204
- tyrosine hydroxylase
Repeated administration of methamphetamine (mAMPH) to rodents in a single-day “binge” produces long-lasting damage to dopaminergic and serotonergic terminals. Because previous research has demonstrated that physical activity can ameliorate nigrostriatal injury, this study investigated whether voluntary exercise in rats can alter the monoaminergic damage resulting from a neurotoxic mAMPH binge. Adult male rats were allowed constant access to running wheels or kept in nonwheel cages for three weeks, then given a binge dosing regimen of mAMPH or saline. The rats were returned to their original environments for three additional weeks post-mAMPH. [125I]RTI-55 binding and autoradiography was used to quantify dopamine transporters (DAT), and radioimmunocytochemistry was used to quantify striatal tyrosine hydroxylase (TH). Binge mAMPH treatment significantly reduced striatal DAT and TH in a regionally specific pattern; with greatest effects in ventral caudate-putamen (CP) and relative sparing of the nucleus accumbens septi (NAc). The effects of mAMPH on striatal DAT and TH were ameliorated in the running, compared to the sedentary, animals. Also, mAMPH was found to reduce [125I]RTI-55 binding to serotonin transporters (SERT) in frontoparietal cortex, and this too was significantly attenuated by exercise. Additional correlational analyses showed that the post-mAMPH running of individual animals predicted the amelioration of striatal DAT and TH as well as frontoparietal SERT. Overall, voluntary exercise significantly diminished mAMPH-induced forebrain monoaminergic damage. The significant correlations between post-mAMPH exercise and markers of monoaminergic terminal integrity provide novel evidence that voluntary exercise may exert beneficial effects on behavior in recovering mAMPH addicts. Synapse, 2012. © 2011 Wiley Periodicals, Inc.