EFFECT OF DRUGS ON THE UPTAKE, RELEASE, AND METABOLISM OF H³-NOREPINEPHRINE IN THE RAT BRAIN

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

The effects of drugs and metabolic inhibitors on the uptake, release and metabolism of intraventricularly administered H³-norepinephnine in the rat brain are described. Amphetamine, reserpine and guanethidine, but not cocaine, D-lysergic acid diethylamide, mescaline or bretylium, block the uptake or accumulation of H³-norepinephrine in the brain. Monoamine oxidase inhibition produces an elevation of H3-norepinephrine and H³-normetanephrine in the brain. A catechol O-methyl transferase inhibitor, tropolone-4-acetamide, reduces the level of H3-normetanephrine but has no effect on the level of H³-norepinephrine. Amphetamine and reserpine release H³-norepinephrine in a different manner. Amphetamine administration results in an elevation of normetanephrine levels, while reserpine administration causes an elevation of O-methylated deaminated metabolites. Both drugs release a greater proportion of the brain content of H³-norepinephrine when they are administered a long time after the injection of the radioactive catecholamine than after a short time. The different actions of amphetamine and reserpine on the metabolism of H3-norepinephrine indicate the presence of more than one storage form of the brain catecholamine.

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