Mouse strain-dependent effect of amantadine on motility and brain biogenic amines.
The effect of amantadine hydrochloride, injected i.p. in 6 increments of 100 mg/kg each over 30 hr, on mouse motility and whole brain content of selected biogenic amines and major metabolites was studied in 4 strains of mice. These were the albino Sprague-Dawley ICR and BALB/C, the black C57BL/6 and the brown CDF-I mouse strains. Amantadine treatment produced a biphasic effect on mouse motility. The initial dose of amantadine depressed locomotor activity in all mouse strains studied with the BALB/C mice being the most sensitive. Subsequent amantadine treatments produced enhancement of motility from corresponding control in all mouse strains with the BALB/C mice being the least sensitive. The locomotor activity was decreased from corresponding controls in all strains studied, except for the ICR mice, during an overnight drug-free period following the fourth amantadine treatment. Readministration of amantadine, after a drug-free overnight period, increased motility from respective saline control in all strains with exception of the BALB/C mice where suppression of motility occurred. Treatment with amantadine did not alter whole brain dopamine levels but decreased the amounts of 3,4-dihydroxyphenylacetic acid in the BALB/C mice compared to saline control. Conversely, brain normetanephrine concentration was increased from saline control by amantadine in the BALB/C mice. The results suggest a strain-dependent effect of amantadine on motility and indicate a differential response to the acute and multiple dose regimens used. The BALB/C mouse was the most sensitive strain and could serve as the strain of choice for evaluating the side effects of amantadine. The biochemical results of brain biogenic amines of BALB/C mouse strain suggest a probable decrease of catecholamine turnover rate and/or metabolism by monoamine oxidase and a resulting increase in O-methylation of norepinephrine which may account for a behavioral depression caused by amantadine in the BALB/C mice.
Messiha
F S
FS
Department of Pharmacology, School of Medicine, University of North Dakota, Grand Forks 58203.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000547:Amantadine / Q000494:pharmacology*; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D013045:Species Specificity
D001679:Biogenic Amines; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D000547:Amantadine; D004298:Dopamine; D006719:Homovanillic Acid