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Neuropharmacology. 2015 Jun;93:146-54. doi: 10.1016/j.neuropharm.2015.01.013. Epub 2015 Jan 31.

Prior methamphetamine self-administration attenuates the dopaminergic deficits caused by a subsequent methamphetamine exposure.

Author information

1
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112, United States.
2
School of Dentistry, University of Utah, Salt Lake City, UT 84112, United States.
3
School of Dentistry, University of Utah, Salt Lake City, UT 84112, United States. Electronic address: fleckenstein@hsc.utah.edu.

Abstract

Others and we have reported that prior methamphetamine (METH) exposure attenuates the persistent striatal dopaminergic deficits caused by a subsequent high-dose "binge" METH exposure. The current study investigated intermediate neurochemical changes that may contribute to, or serve to predict, this resistance. Rats self-administered METH or saline for 7 d. On the following day (specifically, 16 h after the conclusion of the final METH self-administration session), rats received a binge exposure of METH or saline (so as to assess the impact of prior METH self-administration), or were sacrificed without a subsequent METH exposure (i.e., to assess the status of the rats at what would have been the initiation of the binge METH treatment). Results revealed that METH self-administration per se decreased striatal dopamine (DA) transporter (DAT) function and DA content, as assessed 16 h after the last self-administration session. Exposure to a binge METH treatment beginning at this 16-h time point decreased DAT function and DA content as assessed 1 h after the binge METH exposure: this effect on DA content (but not DAT function) was attenuated if rats previously self-administered METH. In contrast, 24 h after the binge METH treatment prior METH self-administration: 1) attenuated deficits in DA content, DAT function and vesicular monoamine transporter-2 function; and 2) prevented increases in glial fibrillary acidic protein and DAT complex immunoreactivity. These data suggest that changes 24 h, but not 1 h, after binge METH exposure are predictive of tolerance against the persistence of neurotoxic changes following binge METH exposures.

KEYWORDS:

Dopamine; Methamphetamine; Self-administration; Striatum; Tolerance

PMID:
25645392
PMCID:
PMC4387067
DOI:
10.1016/j.neuropharm.2015.01.013
[Indexed for MEDLINE]
Free PMC Article

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