The effects of methamphetamine self-administration on cortical monoaminergic deficits induced by subsequent high-dose methamphetamine administrations
Article first published online: 27 JUL 2013
Copyright © 2013 Wiley Periodicals, Inc.
Volume 67, Issue 12, pages 875–881, December 2013
How to Cite
Mcfadden, L. M., Hanson, G. R. and Fleckenstein, A. E. (2013), The effects of methamphetamine self-administration on cortical monoaminergic deficits induced by subsequent high-dose methamphetamine administrations. Synapse, 67: 875–881. doi: 10.1002/syn.21696
- Issue published online: 15 OCT 2013
- Article first published online: 27 JUL 2013
- Accepted manuscript online: 3 JUL 2013 05:51AM EST
- Manuscript Accepted: 25 JUN 2013
- Manuscript Received: 26 FEB 2013
- NIH. Grant Numbers: DA033097, 011389, 019447, 000378, 013367, 031883
Preclinical models suggest that repeated high-dose methamphetamine (METH) exposures, administered in a “binge-like” pattern, acutely decrease norepinephrine (NE), and acutely and persistently decrease serotonin (5-hydroxytryptamine; 5HT) content in the frontal cortex. However, the impact of METH self-administration on this region is unknown. Because of the importance of the monoaminergic neurons in the frontal cortex to a variety of cognitive and addictive processes, effects of METH self-administration on cortical NE and 5HT content were assessed. Results revealed several novel findings. First, METH self-administration decreased cortical NE content as assessed 24 h after last exposure. Consistent with previous preclinical reports after a binge METH regimen, this decrease was reversed 8 days after the final METH exposure. Second, and in contrast to our previous reports involving the hippocampus or striatum, METH self-administration caused persistent decreases in 5HT content as assessed 8 days after the final METH exposure. Of note, the magnitude of this decrease (∼20%) was less than that observed typically after a binge METH treatment. Third, prior METH self-administration attenuated METH-induced serotonergic deficits as assessed 7 days, but not 1 h, following a neurotoxic METH regimen. No protection was observed when the binge exposure occurred 15 days after the last self-administration session. Taken together, these data demonstrate important and selective alterations in cortical serotonergic neuronal function subsequent to METH self-administration. These data provide a foundation to investigate complex questions involving “resistance” to the persistent deficits caused by neurotoxic METH exposure and frontal cortical function. Synapse 67:875–881, 2013. © 2013 Wiley Periodicals, Inc.