STORAGE AND SYNTHESIS OF NOREPINEPHRINE IN THE RESERPINE-TREATED RAT BRAIN

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

The retention of H³-norepinephrine in the rat brain after the injection of H³-norepinephrine into the lateral ventricle of the brain was severely reduced 6 hr after a single injection of reserpine. The ability to retain small amounts of H³-norepinephrine in the brain recovered rapidly between 24 and 48 hr after reserpine at a time when the animals were recovering from the most obvious behavioral effects of the drug. During this period the endogenous norepinephrine content of the brain was markedly depressed and rose only slowly to 40% of normal levels after 8 days. In reserpine-treated rat brains the accumulation of H³-norepinephrine could be inhibited by pretreatment with a second dose of reserpine or increased by treatment with an inhibitor of monoamine oxidase. Treatment of reserpinized animals with amphetamine or DMI produced changes in the metabolism of H³-norepinephrifle which indicate that these drugs are still able to inhibit norepinephrine uptake in such animals. These results are consistent with other studies which suggest that the primary action of reserpine is to impair the intracellular storage of norepinephrine rather than to inhibit the uptake of norepinephrine into adrenergic neurons. The small amount of H³-norepinephrine retained in the brains of 24-hr reserpinized animals was resistant to release by amphetamine or by the administration of an additional dose of reserpine. After the administration of C¹⁴-tyrosine or H³-dopamine into the lateral ventricle of normal or reserpinized rat brains it was possible to demonstrate that all the enzymatic steps involved in the biosynthesis of norepinephrine can occur in reserpinized animals.

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