Differential neurochemical consequences of an escalating dose-binge regimen followed by single-day multiple-dose methamphetamine challenges

• Published in: Journal of neurochemistry 2008-06, Vol.105 (5), p.1873-1885
• Main Authors: Graham, Devon L, Noailles, Pierre-A.H, Cadet, Jean Lud
• Format: Article
• Language: English
• Subjects: Amphetamine-Related Disorders - metabolism; Animals; Biochemistry; Biological and medical sciences; Brain Chemistry - drug effects; Brain Chemistry - physiology; dopamine; Dopamine - metabolism; Dose-Response Relationship, Drug; Drug abuse; Drug addictions; Drug Administration Schedule; Male; Medical sciences; Methamphetamine; Methamphetamine - administration & dosage; Methamphetamine - toxicity; Neurology; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Rodents; serotonin; tolerance; toxicity; Toxicology; turnover
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2008.05269.x

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.