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.
Maura
G
G
Bonanno
G
G
Raiteri
M
M
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology*; D006207:Half-Life; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism
D011942:Receptors, Adrenergic, alpha; D012701:Serotonin; D011189:Potassium Chloride; D003000:Clonidine; D009638:Norepinephrine