Methylphenidate and pemoline do not cause depletion of rat brain monoamine markers similar to that observed with methamphetamine.
Methylphenidate (Ritalin) and pemoline (Cylert) are central nervous system stimulants which are widely prescribed for attention deficit and other psychiatric disorders. Several other related stimulants, including amphetamine and methamphetamine, have been shown to cause long lasting decreases in monoamine markers in rat brain, characteristic of axonal degeneration. To assess the neurotoxic potential of methylphenidate and pemoline, we compared the effects of multiple injections (sc, bid for up to 4 days) of methylphenidate (21 and 50 mg/kg) and pemoline (20 and 70 mg/kg) with methamphetamine (5 and 15 mg/kg) on rat brain norepinephrine, dopamine, and serotonin levels and transport sites. While decreases were observed in all brain monoamine markers measured in rats treated with methamphetamine, no changes were observed in animals treated with methylphenidate as compared to saline-treated controls. Pemoline failed to induce significant changes in the level of monoamine transport sites; however, a wide array of changes were observed in the levels of 5-hydroxyindoleacetic acid, dopamine, and norepinephrine in various brain areas after a 3-day treatment regimen with a high dose (70 mg/kg) of pemoline. The lack of changes in monoamine transport sites following the repeated administration of high doses of methylphenidate and pemoline suggests that these drugs do not affect axonal integrity. However, the pattern of changes observed in the levels of monoamines after pemoline treatment may have relevance to the self-injurious behavior seen in these animals.
Zaczek
R
R
Neuroscience Branch, National Institute on Drug Abuse, Baltimore, Maryland 21224.
Battaglia
G
G
Contrera
J F
JF
Culp
S
S
De Souza
E B
EB
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015306:Biogenic Monoamines / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D008774:Methylphenidate / Q000633:toxicity*; D009638:Norepinephrine / Q000378:metabolism; D010389:Pemoline / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012652:Self Mutilation / Q000139:chemically induced; D012701:Serotonin / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
D015306:Biogenic Monoamines; D015415:Biomarkers; D008774:Methylphenidate; D012701:Serotonin; D008694:Methamphetamine; D010389:Pemoline; D004298:Dopamine; D009638:Norepinephrine