Mouse Strain Sensitivity to Chlorpromazine and Amantadine Interaction

Abstract

Amantadine, a dopaminergic agonist, has been used in the management of neurolepticinduced dyskinesia and in Tourette’s syndrome. Genetic predisposition has been implicated in both of these movement disorders with a possible underlying abnormality in cerebral biogenic amine function. The effect of repeated administration of amantadine prior to chlorpromazine therapy on motor activity, whole brain dopamine, 5-hydroxytryptamine (5-HT, serotonin) and some major metabolites was studied as a function of mouse strain. Chlorpromazine-enhanced amantadine therapy produced increases in motor activity in outbred albino ICR mice but not in inbred BALB/c mice. Combined drug treatment prevented chlorpromazine-mediated reduction of brain dopamine, suggesting that amantadine antagonises this effect. Amantadine counteracted chlorpromazine-induced increases of BALB/c but not ICR mouse brain 5-hydroxyindoleacetic acid. This interaction may be useful in investigating the suggested imbalance between catecholamine and indoleamine systems implicated in drug-induced tremors and extrapyramidal disorders. The results suggest a genotypic-dependent amantadine-chlorpromazine interaction involving motor function and brain monoamines that may underlie individual susceptibility to the development of neuroleptic-induced dyskinesia and/or the variable responses to amantadine therapy in patients with tardive dyskinesia or Tourette’s syndrome.