Recent experiments have shown that mice lacking the α1b‐adrenergic receptor (α1b‐AR KO) are less responsive to the locomotor hyperactivity induced by psychostimulants, such as D‐amphetamine or cocaine, than their wild‐type littermates (WT). These findings suggested that psychostimulants induce locomotor hyperactivity not only because they increase dopamine (DA) transmission, but also because they release norepinephrine (NE). To test whether NE release could increase DA‐mediated locomotor hyperactivity, rats were treated with GBR 12783 (10 mg/kg), a specific inhibitor of the DA transporter, and NE release was enhanced with dexefaroxan (0.63–10 mg/kg), a potent and specific antagonist at α2‐adrenergic receptors. Dexefaroxan increased the GBR 12783‐mediated locomotor response by almost 8‐fold. The role of α1b‐ARs in this effect was then verified in α1b‐AR KO mice: whereas dexefaroxan (1 mg/kg) doubled locomotor hyperactivity induced by GBR 12783 (14 mg/kg) in WT mice, it decreased it by 43% in α1b‐AR KO mice. Finally, to test whether this latter inhibition was related to the occupation of α2‐adrenergic autoreceptors or of α2‐ARs not located on noradrenergic neurons, effects of dexefaroxan on locomotor hyperactivity induced by D‐amphetamine (0.75 mg/kg) were monitored in rats depleted in ascending noradrenergic neurons. In these animals dexefaroxan inhibited by 25–70% D‐amphetamine‐induced locomotor hyperactivity. These data indicate not only that the stimulation of α1b‐ARs increases DA‐mediated locomotor response, but also suggest a significant implication of postsynaptic α2‐ARs. Involvement of these adrenergic receptor mechanisms may be exploited in the therapy of Parkinson's disease. Synapse 50:277–284, 2003. © 2003 Wiley‐Liss, Inc.

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   |texte=   Stimulation of postsynaptic α1b‐ and α2‐adrenergic receptors amplifies dopamine‐mediated locomotor activity in both rats and mice
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