Pharmacological evidence for a stimulation of dopamine neurons by noradrenaline neurons in the brain.

The effects of yohimbine (3 mg/kg i.p.), phenoxybenzamine (20 mg/kg i.p.) and clonidine (0.1 mg/kg i.p.) on the synthesis and the utilization of dopamine and noradrenaline in the central nervous system of rats were investigated. Dopa accumulation following decarboxylase inhibition and the alpha-methyltyrosine-induced disappearance of the amines were used as the measure of these effects. The synthesis and the utilization of dopamine and noradrenaline were accelerated by yohimbine. Clonidine plus phenoxybenzamine inhibited the synthesis and utilization of dopamine and the combination also partly antagonized the effects of yohimbine on the trunover of dopamine. The effects of the three drugs on the synthesis and utilization of dopamine might be secondary to their actions on alpha-adrenoreceptors of noradrenaline synapses since, at the doses used, yohimbine increases the release of noradrenaline, phenoxybenzamine blocks postsynapptic noradrenaline receptors and clonidine reduces the release of noradrenaline. This hypothesis is supported by the findings that yohimbine and phenoxybenzamine did not change the increased synthesis of dopamine in reserpine-treated rats and that clonidine did not inhibit the increased synthesis of dopamine after axotomy or treatment with reserpine.