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

Lisa M. McFadden, Paula L. Vieira-Brock, Glen R. Hanson, Annette E. Fleckenstein

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)146-154
Number of pages9
StatePublished - Jun 2015
Externally publishedYes


  • Dopamine
  • Methamphetamine
  • Self-administration
  • Striatum
  • Tolerance

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience


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