title: Prior methamphetamine self-administration attenuates the dopaminergic deficits caused by a subsequent methamphetamine exposure.
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.
authors: Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112, United States.
authors: Lisa M
authors: LM
authors: McFadden
authors: Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112, United States.
authors: Paula L
authors: PL
authors: Vieira-Brock
authors: School of Dentistry, University of Utah, Salt Lake City, UT 84112, United States.
authors: Glen R
authors: GR
authors: Hanson
authors: School of Dentistry, University of Utah, Salt Lake City, UT 84112, United States. Electronic address: fleckenstein@hsc.utah.edu.
authors: Annette E
authors: AE
authors: Fleckenstein
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000172:deficiency* / Q000493:pharmacokinetics; D015259:Dopamine Agents / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D013997:Time Factors; D014316:Tritium / Q000493:pharmacokinetics; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
chemical_list: D015259:Dopamine Agents; D005904:Glial Fibrillary Acidic Protein; C493454:Slc18a2 protein, rat; D050493:Vesicular Monoamine Transport Proteins; D014316:Tritium; D015102:3,4-Dihydroxyphenylacetic Acid; D008694:Methamphetamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
keywords: Dopamine; Methamphetamine; Self-administration; Striatum; Tolerance
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