REGIONAL STUDIES OF CATECHOLAMINES IN THE RAT BRAIN. IV. EFFECTS OF DRUGS ON THE DISPOSITION AND METABOLISM OF H³-NOREPINEPHRINE AND H³-DOPAMINE

¹ Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland

The effects of reserpine, a monoamine oxidase inhibitor, Catron (pheniprazine), amphetamine and desmethylimipramine (DMI) on the metabolism of dl-H³-norepinephrine were examined in cerebellum, medulla oblongata, hypothalamus, striatum, midbrain, hippocampus and cortex of the rat brain. Reserpine reduced the accumulation of H⁸-norepinephrine to varying extents in the different brain regions. In reserpine-pretreated animals, there was also an elevation in the levels of H³-deaminated metabolites and a fall in H³-normetanephrine in all regions. After Catron, there was an increased accumulation of H³-norepinephrine in all areas of the brain except in the striatum; deaminated metabolites were severely reduced, while H³-normetanephrine levels were strikingly elevated in all areas of the brain, including the striatum. Both amphetamine and DMI reduced the accumulation of H³- norepinephrine in the cerebellum, medulla oblongata and hypothalamus, but produced only small changes in other areas. Amphetamine caused a striking elevation in the levels of H³-normetanephrine throughout the brain, while DMI produced only small elevations in the medulla oblongata and cortex. O-methylated deaminated metabolites were unaffected by either drug, though catechol deaminated metabolites were reduced, particularly after amphetamine. H³-amphetamine was evenly distributed in the brain at a concentration of about 8 µg/g (5 x 10^-3M) after an intraperitoneal injection of 15 mg/kg. Amphetamine at this concentration almost completely inhibited the enzymatic deamination of H³-norepinephrine in vitro. The levels of H³-norepinephrine were reduced in the medulla oblongata, cerebellum and hypothalamus after the intraventricular injection of H³-dopamine in d- amphetamine- or DMI-pretreated animals. H³-dopamine levels in these regions and in the striatum were unaffected or increased after amphetamine or DMI.

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