title: Comparison of the effects of methamphetamine, bupropion, and methylphenidate on the self-administration of methamphetamine by rhesus monkeys.
abstract: The effectiveness of methadone as a treatment for opioid abuse and nicotine preparations as treatments for tobacco smoking has led to an interest in developing a similar strategy for treating psychostimulant abuse. The current study investigated the effects of three such potential therapies on intravenous methamphetamine self-administration (1 - 30 μg/kg/injection) in rhesus monkeys. When given as a presession intramuscular injection, a high dose of methamphetamine (1.0 mg/kg) decreased intravenous methamphetamine self-administration but did not affect responding for a food reinforcer during the same sessions. However, the dose of intramuscular methamphetamine required to reduce intravenous methamphetamine self-administration exceeded the cumulative amount taken during a typical self-administration session, and pretreatment with a low dose of methamphetamine (0.3 mg/kg) actually increased self-administration in some monkeys at the lower self-administration dose. Like pretreatment with methamphetamine, pretreatment with bupropion (3.2 mg/kg) decreased methamphetamine self-administration but did not affect responding for food. Pretreatment with methylphenidate (0.56 mg/kg) did not significantly alter methamphetamine self-administration. These results suggest that some agonist-like agents can decrease methamphetamine self-administration. Although the most robust effects occurred with a high dose of methamphetamine, safety and abuse liability considerations suggest that bupropion should also be considered for further evaluation as a methamphetamine addiction treatment.
authors.affiliation: Preclinical Pharmacology Section, NIH/NIDA Intramural Research Program, 251 Bayview Boulevard, Suite 200, Baltimore, MD 21224, USA. cschindl@helix.nih.gov
authors.forename: Charles W
authors.initials: CW
authors.lastname: Schindler
authors.forename: Joanne P
authors.initials: JP
authors.lastname: Gilman
authors.forename: Leigh V
authors.initials: LV
authors.lastname: Panlilio
authors.forename: David J
authors.initials: DJ
authors.lastname: McCann
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goldberg
mesh_terms: D000818:Animals; D016642:Bupropion / Q000009:adverse effects / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects; D008253:Macaca mulatta; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D008774:Methylphenidate / Q000009:adverse effects / Q000494:pharmacology*; D009042:Motivation; D012646:Self Administration; D019966:Substance-Related Disorders / Q000188:drug therapy*
chemical_list: D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D016642:Bupropion; D008774:Methylphenidate; D008694:Methamphetamine