INHIBITION OF CATECHOLAMINE SYNTHESIS WITH ALPHA-METHYL-P-TYROSINE APPARENTLY INCREASES BRAIN SEROTONINERGIC ACTIVITY IN THE RAT - NO INFLUENCE OF PREVIOUS CHRONIC IMMOBILIZATION STRESS

The functional relationship between brain catecholamines and serotonin ergic function was studied in stress-naive and chronically immobilized rats after blockade of catecholamine synthesis with alpha-methyl-p-ty rosine (alpha MpT). The levels of noradrenaline (NA), serotonin, and 5 -hydroxyindole acetic acid (5-HIAA) in pens plus medulla, brainstem, h ypothalamus, hippocampus, and frontal cortex, and those of 3-methoxy, 4-hydroxypheniletileneglicol sulphate (MHPG-SO4) in the hypothalamus w ere measured by HPLC. Chronic immobilization (IMO) resulted in higher NA levels in pens plus medulla and hypothalamus, the latter area (the only one in which the NA metabolite was determined) also showing sligh tly elevated MHPG-SO4 levels as compared to stress-naive rats. Chronic IMO did not alter either serotonin or 5-HIAA levels, but acute stress consistently increased 5-HIAA levels in all areas, independently of p revious chronic stress. Administration of alpha-MpT drastically reduce d NA and increased 5-HIAA levels in all brain regions excepting the fr ontal cortex. The effect of the drug on serotoninergic function was no t altered by previous chronic exposure to IMO. These data suggest that the noradrenergic system appears to exert a tonic inhibitory effect o n serotoninergic activity in the brain, with the intensity of the effe ct depending on the brain area studied. In addition, chronic stress do es not appear to alter the functional relationship between noradrenerg ic and serotoninergic activities, although interactions might exist in more restricted brain areas; this deserves further study.