Effects of amitriptyline and nortriptyline on cerebral activity of the CDF-1 mouse strain

1. Equal dose regimens of amitriptyline, a tertiary amine tricyclic antidepressant, were more potent than nortriptyline, a secondary amine derivative, in suppressing CDF-1 mouse locomotor activity. 2. A suggestive increase in dopamine turnover rate in mouse cerebral cortex and striatal brain regions was apparent by amitriptyline but not nortriptyline. 3. A suggestive increase in serotonin turnover in mouse cerebellum and striatum was determined for nortriptyline. 4. Both antidepressants increased cerebral cortex, midbrain and cerebellum serotonin levels from saline control. 5. Increases of regional brain dopamine by amitriptyline and serotonin by nortriptyline concurrent with reuptake blockade of the respective serotonin and dopamine may contribute to their differential extrapyramidal and sedating side effects.