The Relationship of the Synthesis and Metabolism of Catecholamines to Brain Function

Abstract

The three principle monoamines dopamine (DA) noradrenaline (NA) and 5-hydroxytryptamine (5-HT) are widely distributed throughout the CNS. These neuromodulator substances are known to affect neuronal excitability at the single cell level (1), as well as to influence the output of large networks of neurons (2). At present, there is considerable uncertainty about how the processes of synthesis, release and metabolism are regulated in monoaminergic neurons. In the periphery, reuptake is the main mechanism of transmitter conservation (3, 4). In the CNS, similar reuptake mechanisms have been demonstrated for the monoamines (5, 6). However, in recent years, the concept that reuptake may play a primary role in transmitter conservation has been largely ignored. Instead we have come to focus on the idea that the released transmitter is largely catabolized. This hypothesis has, in turn, led to a number of corollary beliefs, most of which have been supported by published evidence. Among these beliefs are: 1) Levels of metabolities (DOPAC, HVA, MHPG, 5-HIM) are indices of transmitter release, and by implication, neuronal firing. 2) Synthesis is activated during release. 3) Precursor availability may become a limiting factor in transmitter synthesis, during episodes of increased neuronal firing/release. 4) Differences in turnover rates (TR) of monoamines, are indicative of the rates of neuronal firing/ transmitter release in those regions. For a further discussion of these problems, see (7). The purpose of this short review is to explore selective aspects of the questions raised above. Data published in recent years, roughly since 1985, suggest that the interpretation of results referred to above may have been too simplistic. A working model will be presented as a first step in the effort to arrive at a correct understanding of monamine neurotransmitter dynamics, within a functional context.