Autoreceptor Regulation of Dopamine Synthesis

The first evidence for the modulation of dopamine (DA) synthesis by presynaptic dopamine receptors was presented in 1972 by Carlsson and coworkers, who observed that when impulse flow in nigrostriatal DA neurons is interrupted by axotomy the rate of tyrosine hydroxylation in striatal terminals is increased.’ This was interpreted as suggestive of the existence of a presynaptic site at which released DA can act to exert feedback inhibition on DA synthesis. At the time, the concept of autoregulation in the central nervous system (CNS) was novel. Since then, it has become clear that autoreceptors provide a means for many types of neurons to regulate cellular functions such as neurotransmitter release, synthesis, and impulse flow. Although the popularity of DA autoreceptors has waxed and waned over the years, autoreceptor reviews have been plentiful (see Reference 2 for a recent example). This paper will therefore be quite selective in its focus. First, it will concentrate on the autoreceptor regulation of DA synthesis, since release and impulse flow are being discussed by other authors in the volume. Second, the emphasis will be on new developments in this field.