Chronic effects of mianserin on noradrenaline metabolism in the rat brain: evidence for a pre-synaptic alpha-adrenolytic action in vivo.

Chronic administration of the pre-synaptic alpha-adrenoreceptor agonist clonidine decreases the concentration of the extra-neuronal metabolite of noradrenaline normetanephrine in the amygdaloid cortex and increases it in the mid-brain. Conversely, blockade of these pre-synaptic receptors by yohimbine increases the normetanephrine concentration in the amygdaloid cortex and decreases it in the mid-brain. Mianserin had a qualitatively similar action to that of yohimbine. When given clinically to rats in combination with clonidine, mianserin antagonizes both the depression of behaviour of the rats in the 'open field' apparatus and also the effects of the alpha-agonist in reducing the concentration of normetanephrine in the amygdaloid cortex. It thus appears that the chronic effects of mianserin are due to an increase in noradrenaline release as a consequence of the inhibitation of pre-synaptic alpha-adrenoreceptors.