Acute and chronic effects of 4-chloroamphetamine on monoamine metabolism in the rat brain

The acute administration of 4-chloroamphetamine caused a marked reduction in the concentration of serotonin and 5-hydroxyindoleacetic acid and a rise in dopamine in the rat brain. Following the injection of 3H-tyrosine and 3H-tryptophane into rats treated with 4-chloroamphetamine, there was a reduction in brain levels of 3H-dopamine and 3H-serotonin. Although the endogenous concentration of noradrenaline was not affected by 4-chloroamphetamine, there is evidence that its reuptake into neurones was reduced and its release increased by the drug. Following the administration of 4-chloroamphetamine for 10 days, the concentration of 5-hydroxyindoleacetic acid was reduced; no other changes in amine metabolism were apparent. From this investigation, and those of others, it appears that following acute administration, 4-chloroamphetamine has a neurochemical profile which has a similarity to that of many tricyclic antidepressants. However, there is a marked discrepancy between the acute and chronic effects of 4-CA on brain amine metabolism. Such findings are difficult to reconcile with the widely accepted theory that antidepressant drugs counteract the symptoms of depression by increasing the concentration of noradrenaline and/or serotonin at receptor sites within the brain.