Studies on the relationship between the analgesic activity of salicylic acid and the brain catecholamines in mice.

: The catecholamine content in the mouse brain has been investigated after administration of analgesic doses of salicylic acid. Doses of 300 and 450 mg/kg salicylic acid given orally did not produce any significant changes in brain noradrenaline or dopamine levels in comparison with untreated or placebo treated animals. After inhibition of the rate limiting step of the catecholamine synthesis, salicylic acid in a dose of 300 mg/kg administered orally produced significant acceleration in the decrease of brain noradrenaline induced by the synthesis inhibitor. This acceleration was significantly greater in mice showing analgesic activity and in these animals a significant acceleration was also found in brain dopamine. Furthermore, after inhibition of dopamine β-hydroxylase with disulfiram, salicylic acid produced a significant reduction of the brain noradrenaline in animals showing analgesic activity. No corresponding changes were found in dopamine concentrations. The results obtained are similar to those obtained with morphine and it seems possible that salicylates may exert a part of their central analgesic action by interference with noradrenergic or dopamin-ergic neurons. The investigations also showed that the analgesic test procedure used and the manner of injection did not seem to evoke any stress in the animals sufficient to produce changes in the turnover rate of brain noradrenaline or dopamine.