α2A-adrenoceptors enhance the serotonergic effects of fluoxetine

The ability of subtype-preferring α2-adrenoceptor antagonists to enhance the neurochemical effects of the antidepressant, fluoxetine, was evaluated by in vivo microdialysis. Combining the selective α2A-adrenoceptor antagonist, BRL-44408 (10 mg/kg, s.c.), with fluoxetine (30 mg/kg, s.c.) elevated the extracellullar levels of serotonin (5-HT) and noradrenaline in the rat frontal cortex, an effect not observed following antidepressant treatment alone. In contrast, combining fluoxetine with the α2B- or α2C-adrenoceptor antagonists, imiloxan (10 mg/kg, s.c.) or rauwolscine (10 mg/kg, s.c.), respectively, did not similarly alter biogenic amine levels. Collectively, these results reveal a specific role for the α2A-adrenoceptor subtype in augmenting the neurochemical effects of antidepressants.