APPLICATION OF STEADY STATE KINETICS TO THE SYNTHESIS RATE AND TURNOVER TIME OF SEROTONIN IN THE BRAIN OF NORMAL AND RESERPINE-TREATED RATS

Abstract

A new method of measuring the rate of synthesis of brain serotonin (5-HT) takes advantage of the steady state relationship in which the molar rates of 5-HT synthesis and 5-hydroxyindoleacetic acid (5-HIAA) efflux are equal. The method is based on the dynamic steady state of 5-HT and its metabohte 5-HIAA, with rates of formation equal to rates of metalbolism and elimination. After monoamine oxidase was blocked with a number of inhibitors, including pargyline and tranylcypromine, the brain levels of 5-HIAA decline exponentially. The rate of synthesis of 5-HT is calculated from the product of the rate constant of 5-HIAA decline and the normal 5-HIAA level. After depletion of 5-HT stores by reserpine, the 5-HT synthesis rate is not decreased; in fact, the rate possibly may be increased. In the brain stem, 5-HT is formed twice as rapidly as in the rest of the brain, although the rate constants of 5-HIAA efflux are almost identical. This suggests that the rate of synthesis might be similar in each serotonergic unit, and that variations in rates of synthesis in different brain areas are a function of the number of neurons per gram of tissue.