Effects of amphetamine and sydnocarb on dopamine release and free radical generation in rat striatum.
Microdialysis technique was used to compare the effects of four repeated intraperitoneal administrations of two psychostimulant drugs, D-amphetamine and sydnocarb, at the equimolar doses 5 and 23.8 mg/kg, respectively, on the extracellular level of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and hydroxyl radicals (.OH) in the dorsal striatum of freely moving 3-month-old male Wistar rats 250-300 g in weight. D-amphetamine caused immediate increase of DA concentration up to 950% with quick decline towards baseline values thereafter, followed by much less increase after further injections. Sydnocarb elicited moderate elevation in DA level achieving 400% after the fourth injection. D-amphetamine induced deep decrease in DOPAC concentration, while sydnocarb caused its increase after the first and second dosing. Both drugs enhanced generation of .OH, the effect of D-amphetamine was more pronounced. D-Amphetamine induced more intensive stereotyped behavior in rats compare to sydnocarb. It is concluded that the psychostimulant action of sydnocarb is accompanied by facilitation of the central dopaminergic transmission in rat neostriatum and followed by less pronounced neurotoxic effect than that of D-amphetamine.
Afanas'ev
I I
II
Laboratory of Neurochemical Pharmacology, Research Institute of Pharmacology, Russian Academy of Medical Sciences, Baltiyskaya str., 8, Moscow, 125315 Russia.
Anderzhanova
E A
EA
Kudrin
V S
VS
Rayevsky
K S
KS
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology; D013558:Sydnones / Q000494:pharmacology*
D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D005609:Free Radicals; D013558:Sydnones; D015102:3,4-Dihydroxyphenylacetic Acid; D000661:Amphetamine; C009257:sidnocarb; D004298:Dopamine