Alpha 2A-adrenoceptors enhance the serotonergic effects of fluoxetine.
The ability of subtype-preferring alpha(2)-adrenoceptor antagonists to enhance the neurochemical effects of the antidepressant, fluoxetine, was evaluated by in vivo microdialysis. Combining the selective alpha(2A)-adrenoceptor antagonist, BRL-44408 (10 mg/kg, s.c.), with fluoxetine (30 mg/kg, s.c.) elevated the extracellular 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 alpha(2B)- or alpha(2C)-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 alpha(2A)-adrenoceptor subtype in augmenting the neurochemical effects of antidepressants.
Beyer
Chad E
CE
Depression and Anxiety Research, Discovery Neuroscience, Wyeth Research, Princeton, NJ 08543, USA. beyerc1@wyeth.com
Lin
Qian
Q
Rosenzweig-Lipson
Sharon
S
Schechter
Lee E
LE
D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
D058669:Adrenergic alpha-2 Receptor Antagonists; D005473:Fluoxetine; D018341:Receptors, Adrenergic, alpha-2; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors