Determination of Monoamine Turnover by Blockade of Their Synthesis or Metabolism

The neurotransmitter amines, dopamine (DA), norepinephrine (NE), epinephrine (EPI), and serotonin (5-hydroxytrypt-amine, 5-HT) are continuously released and destroyed at various rates, yet their content in neuronal tissue remains relatively constant. Thus, it is not possible to evaluate neuronal function solely from the content of the transmitter in a tissue. A better estimate of neuron function can be obtained from the rate of formation of the amines. The hypothesis is that there is increased amine formation and turnover when neurons are actively firing. Presently, there are two general techniques for estimating the rate of amine formation (see reviews by Costa and Neff, 1970: Neff, 1972; Costa et al., 1975, and Korf 1985). There are the steady-state methods where an isotope-labeled amine (radioactive or stable isotope) or a precursor is administered, and following uptake into nerve endings, the decline of the specific radioactivity of the transmitter is followed with time. The rate of loss of radioactive amine under steady-state conditions is proportional to its turnover. The higher the neuronal firing rate, the faster the rate of decline of the specific radioactivity of the transmitter amine.