Tolerance to the neurotoxic effects of methamphetamine in young rats.
The present study examined whether exposure to methamphetamine during adolescence (as determined in post-natal day 40 rats) might alter its effects when used in young adulthood (as assessed in post-natal day 90 rats). Results confirm that high-dose methamphetamine administration (4x10 mg/kg/injection, s.c., 2-h intervals) decreases striatal dopamine uptake and transporter ligand binding in post-natal day 90 rats; effects that were blocked if animals received six biweekly methamphetamine pretreatments (15 mg/kg; s.c.) beginning at post-natal day 40. This neuroprotection was not likely due to pharmacokinetic tolerance, since brain methamphetamine concentrations did not differ 1 h after the high-dose methamphetamine regimen among treated rats regardless of pretreatment. The methamphetamine biweekly pretreatment attenuated the hyperthermia caused by the neurotoxic methamphetamine regimen; a phenomenon that may have contributed to the neuroprotection.
Riddle
Evan L
EL
University of Utah, Department of Pharmacology and Toxicology, 30 South 2000 East, Room 201, Salt Lake City, UT 84112, USA.
Kokoshka
Jerry M
JM
Wilkins
Diana G
DG
Hanson
Glen R
GR
Fleckenstein
Annette E
AE
D000367:Age Factors; D000818:Animals; D000697:Central Nervous System Stimulants / Q000633:toxicity; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004361:Drug Tolerance; D006979:Hyperthermia, Induced; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D020258:Neurotoxicity Syndromes; D051381:Rats; D017207:Rats, Sprague-Dawley
D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D004298:Dopamine