Chronic clonidine induces functional down-regulation of presynaptic alpha 2-adrenoceptors regulating [3H]noradrenaline and [3H]5-hydroxytryptamine release in the rat brain.

Clonidine inhibited, through the activation of alpha 2 presynaptic receptors, the release of [3H]noradrenaline (pIC30 = 7.47) and [3H]5-hydroxytryptamine (pIC30 = 6.47) evoked by 15 mM KCl from superfused rat cerebral cortex synaptosomes. The natural agonist noradrenaline inhibited the K+-evoked release of the two [3H]amines less effectively after long-term (12 days) treatment with clonidine than after acute treatment. It can be concluded that chronic clonidine administration can induce down-regulation of both the alpha 2 presynaptic autoreceptors located on noradrenaline terminals and the alpha 2 presynaptic heteroreceptors located on serotonin terminals.