EFFECTS OF CATECHOLAMINES ON DOPAMINE AND SEROTONIN SYNTHESIS IN RAT BRAIN STRIATAL SYNAPTOSOMES: THE ROLE OF PRESYNAPTIC RECEPTORS AND THE SYNAPTOSOMAL REUPTAKE MECHANISM.

The regulation of dopamine and serotonin synthesis in rat brain striatal synaptosomes has been studied using HPLC methods. Noradrenaline was shown to markedly inhibit both the synthesis of dopamine and serotonin. The response of the synaptosomes to the concentrations of noradrenaline appeared to be biphasic, a very effective inhibition occurring at low concentrations (1-5 µm) and a relatively ineffective further inhibition occurring at high concentrations (up to 100 µM). The inhibition of dopamine and serotonin synthesis by noradrenaline was also studied in the presence of phenoxybenzamine (alpha adrenergic receptor blocker) and imipramine (reuptake inhibitor). Phenoxybenzamine changed the pattern of inhibition of both dopamine and serotonin synthesis by noradrenaline by preventing the very effective inhibition previously seen at low (1-5 µM) noradrenaline concentrations. Imipramine, whilst showing marked inhibition of dopamine synthesis on its own, prevented any inhibition by noradrenaline. In the case of serotonin synthesis, however, imipramine alleviated some of the inhibition seen in the presence of noradrenaline alone. The results are discussed with respect to the role that presynaptic receptors and reuptake mechanisms play in the regulation of catecholamine and serotonin synthesis at the nerve ending.