Noradrenaline and 5-hydroxytryptamine modulation of brain dopamine function: implications for the treatment of Parkinson's disease.

1 Dopamine deficiency in the brain is the prime biochemical deficit in Parkinson's disease, but loss of noradrenaline and 5HT also may contribute. 2 In rats, 5HT-containing neurones originating from the dorsal and median raphe nuclei innervate forebrain dopamine-containing areas so as to impose an inhibitory regulatory tone on dopamine function. However, this interaction between brain dopamine and 5HT-containing neuronal systems is complex, and the effect produced appears dependent on the relative activity of each system. 3 Anatomical evidence for innervation of dopamine-containing brain regions by noradrenaline fibres in the rat is scanty, but functional studies suggest the existence of inputs which facilitate dopamine function. 4 Drug therapy designed to increase or decrease brain 5HT function has had no consistent effect in Parkinson's disease. 5 Manipulation of brain noradrenergic activity in Parkinson's disease had little effect, although the noradrenaline precursor L-threo-DOPS may reduce freezing attacks. 6 Until more specific drug molecules are available the role of brain noradrenergic and 5HT mechanisms in Parkinson's disease remains uncertain.