7-nitroindazole, nNOS inhibitor, attenuates amphetamine-induced amino acid release and nitric oxide generation but not lipid peroxidation in the rat brain.
The aim of the present study was to elucidate whether amphetamine modulates the output of the neurotransmitters glutamate, aspartate, GABA and acetylcholine (ACh) in nucleus accumbens (NAc) as well as the formation of lipid peroxidation (LPO) and nitric oxide (NO). D,L-amphetamine (AMPH, 5 mg/kg, i.p., 4 times every 2 h) was injected into anaesthetized rats and the release of neurotransmitters in the NAc, tissue content of NO and LPO products were determined. While AMPH increased the release of aspartate, GABA and ACh in the NAc, the glutamate release was not affected. Levels of NO and LPO products were elevated in striatum and cortex. Pretreatment with the neuronal NO synthase inhibitor 7-nitroindazole (50 mg/kg, i.p.) was highly effective in abating the rise of the neurotransmitter release and NO generation but failed to influence the intensity of LPO elicited by the AMPH administration. These findings suggest that activation of NO synthesis is a potent factor in the AMPH-induced neurotransmitter release and that activation of NO synthesis and LPO by AMPH are not parallel processes.
Bashkatova
V
V
Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow, Russia.
Kraus
M M
MM
Vanin
A
A
Hornick
A
A
Philippu
A
A
Prast
H
H
D000596:Amino Acids / Q000096:biosynthesis / Q000187:drug effects*; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000596:Amino Acids; D000697:Central Nervous System Stimulants; D004791:Enzyme Inhibitors; D007191:Indazoles; D018377:Neurotransmitter Agents; D017392:Thiobarbituric Acid Reactive Substances; D009569:Nitric Oxide; D000661:Amphetamine; C080122:7-nitroindazole