[Combined effect of amphetamine and midantan on the dopaminergic transmission in the striatum of freely moving rats].
The combined action of midantane (amantadine, a noncompetitive NMDA receptor antagonist used as an antiparkinsonian drug) and amphetamine (a psychostimulant) on the extracellular level of dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) was studied in the striatum of freely moving Wistar rats. After the administration of amphetamine (AMPH) in a dose of 10 mg/kg (i.p.), the extracellular level of dopamine exhibited a sharp increase in (up to 700% relative to the basal level) within 20-40 min and then gradually decreased. One hour after the injection of AMPH, the content of DOPAC and HVA decreased by 60 and 40%, respectively, and then was retained on this level. Midantane (20 mg/kg, i.p.) injected alone did not influence the level of dopamine and its metabolites. Administered together with AMPH, midantane prevented the extracellular accumulation of dopamine, but did not change the extracellular level of its metabolites reduced by AMPH. These results suggest that NMDA receptor antagonists can block the AMPH-stimulated dopamine release from a vesicular pool, while not affecting the other components of dopamine action such as the re-uptake reversal and inhibition of monoamine oxidase.
Afanas'ev
I I
II
Laboratory of Neurochemical Pharmacology, Institute of Pharmacology, Russian Academy of Medical Sciences, Baltiiskaya Str., 8, Moscow, 125315 Russia.
Dvorkina
M L
ML
Raevskiĭ
K S
KS
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000547:Amantadine / Q000494:pharmacology*; D000661:Amphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013239:Stereotyped Behavior / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D000978:Antiparkinson Agents; D000697:Central Nervous System Stimulants; D016194:Receptors, N-Methyl-D-Aspartate; D015102:3,4-Dihydroxyphenylacetic Acid; D000547:Amantadine; D000661:Amphetamine; D004298:Dopamine; D006719:Homovanillic Acid