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Methamphetamine treatment during development attenuates the dopaminergic deficits caused by subsequent high‐dose methamphetamine administration
Author(s) -
Mcfadden Lisa M.,
Hoonakker Amanda J.,
VieiraBrock Paula L.,
Stout Kristen A.,
Sawada Nicole M.,
Ellis Jonathan D.,
Allen Scott C.,
Walters Elliot T.,
Nielsen Shan M.,
Gibb James W.,
Alburges Mario E.,
Wilkins Diana G.,
Hanson Glen R.,
Fleckenstein Annette E.
Publication year - 2011
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20902
Subject(s) - meth , methamphetamine , dopaminergic , medicine , neurotoxicity , pharmacology , hyperthermia , dopamine , toxicity , chemistry , monomer , organic chemistry , polymer , acrylate
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 duringdevelopment. These findings suggest METH during development prevents METH‐induced hyperthermia and the consequent METH‐related neurotoxicity. Synapse 2011. © 2011 Wiley‐Liss, Inc.