Differential neurochemical consequences of an escalating dose-binge regimen followed by single-day multiple-dose methamphetamine challenges.
Chronic intake of methamphetamine (METH) causes tolerance to its behavioral and subjective effects. To better mimic human patterns of drug abuse, the present study used a rodent model that took into account various facets of human drug administration and measured METH-induced effects on brain monoamine levels. Adult male Sprague-Dawley rats were injected with METH or saline according to an escalating dose schedule for 2 weeks. This was followed by a challenge regimen of either saline or one of two doses of METH (3 x 10 mg/kg every 2 h or 6 x 5 mg/kg given every hour, both given within a single day). Both challenge doses of METH caused significant degrees of depletion of dopamine in the striatum and norepinephrine and serotonin in the striatum, cortex, and hippocampus. Animals pre-treated with METH showed significant attenuation of METH-induced striatal dopamine depletion but not consistent attenuation of norepinephrine and serotonin depletion. Unexpectedly, METH pre-treated animals that received the 3 x 10 mg/kg challenge showed less increases in tympanic temperatures than saline pre-treated rats whereas METH pre-treated animals that received the 6 x 5 mg/kg METH challenge showed comparable increases in temperatures to saline pre-treated rats. Therefore, pre-treatment-induced partial protection against monoamine depletion is probably not because of attenuated METH-induced hyperthermia in those rats.
Graham
Devon L
DL
Molecular Neuropsychiatry Branch, DHHS/NIH/NIDA Intramural Research Program, Baltimore, Maryland 21224, USA.
Noailles
Pierre-A H
PA
Cadet
Jean Lud
JL
D019969:Amphetamine-Related Disorders / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage* / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D008694:Methamphetamine; D004298:Dopamine