Noradrenaline inhibits central serotonin release through alpha2-adrenoceptors located on serotonergic nerve terminals

The effect of noradrenaline on the depolarization-evoked release of 3H-5-hydroxytryptamine was investigated in superfused synaptosomes prepared from rat cortex and hippocampus and prelabelled with the radioactive indoleamine. Noradrenaline reduced in a concentration-dependent way the release of 3H-5-hydroxytryptamine elicited by 15 mM KCl. The inhibition was counteracted by the alpha-adrenoceptor antagonists phentolamine or yohimbine, but not by prazosin. The results indicate that, in rat brain, the inhibition of 5-hydroxytryptamine release by noradrenaline is mediated by adrenoceptors of the alpha 2-type localized on the terminal serotonergic fibres.