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The interaction between clonidine, as an agonist at the alpha 2-autoreceptors regulating noradrenaline release, and inhibitors of noradrenaline neuronal uptake was investigated in superfused synaptosomes, i.e. in conditions preventing accumulation of the released transmitter in the vicinity of presynaptic autoreceptors. Desipramine or cocaine did not release the inhibitory action of clonidine on the release of 3H-noradrenaline evoked by 15 mM KCl from rat cortex synaptosomes, even when the concentration ratio between uptake inhibitor and clonidine was very high. The present results do not support the hypothesis of an interaction between imidazolines and noradrenaline uptake inhibitors at the level of alpha 2-autoreceptors, or that of a functional coupling between presynaptic alpha 2-autoreceptors and noradrenaline uptake mechanism.