Effects of nitric oxide synthesis inhibition on methamphetamine-induced dopaminergic and serotonergic neurotoxicity in the rat brain.
We examined effects of nitric oxide (NO.) synthesis inhibition on methamphetamine (MA)-induced dopaminergic and serotonergic neurotoxicity. The toxic dose of MA (5 mg/kg, sc, x4) significantly decreased contents of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum (ST), and significantly decreased contents of serotonin (5-HT) in the ST, nucleus accumbens (NA) and medial frontal contex (MFC). Coadministration with a NO. synthase inhibitor, N omega-nitro-L-arginine methyl ester (LNAME) (30 mg/kg, i.p., x2), reduced the MA-induced decreases in contents of DA, DOPAC and HVA in the ST, but not reduced the MA-induced decreases in contents of 5-HT in the ST, NA and MFC. These findings suggest that the MA-induced dopaminergic, but not serotonergic neurotoxicity, may be related to the neural process such as NO. formation caused by the activation of postsynaptic DA receptor.
Abekawa
T
T
Department of Psychiatry, Hokkaido University School of Medicine, Sapporo, Japan.
Ohmori
T
T
Koyama
T
T
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D004298:Dopamine / Q000009:adverse effects / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000009:adverse effects / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology
D015306:Biogenic Monoamines; D018765:Dopamine Uptake Inhibitors; D004791:Enzyme Inhibitors; D009498:Neurotoxins; D015102:3,4-Dihydroxyphenylacetic Acid; D009569:Nitric Oxide; D012701:Serotonin; D008694:Methamphetamine; D012965:Sodium Chloride; D019331:NG-Nitroarginine Methyl Ester; D004298:Dopamine; D006719:Homovanillic Acid