Clonidine-induced place preference is mediated by alpha 2-adrenoceptors outside the locus coeruleus.

Clonidine, administered intraperitoneally at doses of 0.05 and 0.5 mg/kg, produced a conditioned place preference when paired with the less preferred compartment. No preference for either compartment was found when a balanced conditioning place preference paradigm was used. Infusion of 6 micrograms/microliters 6-hydroxydopamine in the locus coeruleus, which markedly depleted noradrenaline in terminal regions, did not modify the effect of 0.05 and 0.5 mg clonidine on place preference. The effect of 0.5 mg/kg was prevented by 1 mg/kg idazoxan, an alpha 2-adrenoceptor antagonist, but not by 3 mg/kg prazosin, which blocks alpha 1-adrenoceptors. Idazoxan by itself (at doses from 0.3 to 3 mg/kg) induced a conditioned place preference when paired with the less preferred side. The results suggest that clonidine has motivational properties which serve to attenuate the aversiveness of the less preferred side in a conditioned place preference paradigm. Stimulation of alpha 2-adrenoceptors postsynaptic to noradrenaline-containing neurons seems to be involved.