Methamphetamine rapidly decreases mouse vesicular dopamine uptake: role of hyperthermia and dopamine D2 receptors.
Multiple high-dose administrations of the dopamine-releasing agent, methamphetamine, rapidly and persistently decrease vesicular dopamine uptake in purified vesicles prepared from striata of treated rats. Because important differences in the neurotoxic effects of stimulants have been documented in rats and mice, the purpose of this study was to determine if methamphetamine-induced effects in rats occur in mice and to elucidate mechanisms underlying these effects. Results reveal methamphetamine treatment rapidly decreased mouse striatal vesicular dopamine uptake; a phenomenon associated with a subcellular redistribution of vesicular monoamine transporter-2 (VMAT-2) immunoreactivity. Both methamphetamine-induced hyperthermia and dopamine D2 receptor activation contributed to the stimulant-induced deficits in vesicular dopamine uptake. Unlike methamphetamine, the dopamine reuptake inhibitors, methylphenidate and cocaine, rapidly increased vesicular dopamine uptake. The implications of these phenomena are discussed.
Ugarte
Yvette V
YV
Department of Pharmacology and Toxicology, University of Utah, 30 South 2000 East, Room 201, Salt Lake City, UT 84112, USA.
Rau
Kristi S
KS
Riddle
Evan L
EL
Hanson
Glen R
GR
Fleckenstein
Annette E
AE
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D065127:Dopamine D2 Receptor Antagonists; D006979:Hyperthermia, Induced / Q000379:methods*; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D009479:Neuropeptides; D017448:Receptors, Dopamine D2 / Q000378:metabolism / Q000502:physiology*; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D065127:Dopamine D2 Receptor Antagonists; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D017448:Receptors, Dopamine D2; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D008694:Methamphetamine; D004298:Dopamine