title: Methamphetamine treatment during development attenuates the dopaminergic deficits caused by subsequent high-dose methamphetamine administration.
abstract: Administration of high doses of methamphetamine (METH) causes persistent dopaminergic deficits in both nonhuman preclinical models and METH-dependent persons. Noteworthy, adolescent [i.e., postnatal day (PND) 40] rats are less susceptible to this damage than young adult (PND90) rats. In addition, biweekly treatment with METH, beginning at PND40 and continuing throughout development, prevents the persistent dopaminergic deficits caused by a "challenge" high-dose METH regimen when administered at PND90. Mechanisms underlying this "resistance" were thus investigated. Results revealed that biweekly METH treatment throughout development attenuated both the acute and persistent deficits in VMAT2 function, as well as the acute hyperthermia, caused by a challenge METH treatment. Pharmacokinetic alterations did not appear to contribute to the protection afforded by the biweekly treatment. Maintenance of METH-induced hyperthermia abolished the protection against both the acute and persistent VMAT2-associated deficits suggesting that alterations in thermoregulation were caused by exposure of rats to METH during development. These findings suggest METH during development prevents METH-induced hyperthermia and the consequent METH-related neurotoxicity.
authors.affiliation: Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah 84112, USA. lisa.mcfadden@utah.edu
authors.forename: Lisa M
authors.initials: LM
authors.lastname: McFadden
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Hoonakker
authors.forename: Paula L
authors.initials: PL
authors.lastname: Vieira-Brock
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Stout
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Sawada
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Ellis
authors.forename: Scott C
authors.initials: SC
authors.lastname: Allen
authors.forename: Elliot T
authors.initials: ET
authors.lastname: Walters
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Nielsen
authors.forename: James W
authors.initials: JW
authors.lastname: Gibb
authors.forename: Mario E
authors.initials: ME
authors.lastname: Alburges
authors.forename: Diana G
authors.initials: DG
authors.lastname: Wilkins
authors.forename: Glen R
authors.initials: GR
authors.lastname: Hanson
authors.forename: Annette E
authors.initials: AE
authors.lastname: Fleckenstein
mesh_terms: D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000009:adverse effects; D002849:Chromatography, Gas; D004298:Dopamine / Q000378:metabolism*; D005334:Fever / Q000139:chemically induced; D048788:Growth and Development / Q000187:drug effects; D008297:Male; D013058:Mass Spectrometry; D008694:Methamphetamine / Q000008:administration & dosage* / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D050493:Vesicular Monoamine Transport Proteins / Q000096:biosynthesis
chemical_list: D000697:Central Nervous System Stimulants; C493454:Slc18a2 protein, rat; D050493:Vesicular Monoamine Transport Proteins; D008694:Methamphetamine; D004298:Dopamine