EFFECTS ON BRAIN BIOGENIC-AMINES OF REPEATED TREATMENTS WITH CALCIUM-ANTAGONISTS

Discrete brain sections were obtained from rats once or repeatedly (once a day for 5 days) given i.p. nifedipine, verapamil or diltiazem at doses ranging from 5 to 20 mg/kg. The biogenic amines and metabolites in the hypothalamus, brain-stem, hippocampus, striatum, cortex and thalamus-midbrain were determined by high-performance liquid chromatography with electrochemical detection. The drug-induced changes, displaying regional specificity and differences according to the various compounds, suggested that: (a) serotonergic systems were activated, especially in fasted rats or after repeated treatment; (b) the dopaminergic system of the striatum was inhibited by nifedipine which did reduce the HVA levels and the HVA/DA, as well as the DOPAC/DA, ratio. These effects disappeared after repeated treatment. It was also speculated that the data obtained could be of great interest in view of the possible use of calcium antagonists to treat disorders of the central nervous system.