Effect of addition of yohimbine (alpha-2-receptor antagonist) to the antidepressant activity of fluoxetine or venlafaxine in the mouse forced swim test.
OBJECTIVE
Studies have suggested that alpha(2)-adrenoceptors strongly affect monoaminergic neurotransmission by enhancing not only noradrenergic but also serotonergic firing rates. With this background in mind, the present study was undertaken to monitor the effect of addition of yohimbine (alpha(2)-adrenoceptor antagonist) to the effect of fluoxetine (selective serotonin reuptake inhibitor) or venlafaxine (dual reuptake inhibitors of both serotonin and norepinephrine) in Porsolt's forced swim test (FST) using male Laca strain mice.


METHODS
The immobility period was recorded in mouse FST during a 6-min period. Different doses of fluoxetine or venlafaxine were administered 30 min before exposing the animals to the test procedure. In the combination study, yohimbine (2 mg/kg i.p.) was administered 15 min before the administration of different doses of fluoxetine or venlafaxine.


RESULTS
Fluoxetine (5, 10, 20 and 40 mg/kg) [F = 28.352] or venlafaxine (2, 4, 8 and 16 mg/kg) [F = 17.842] dose-dependently inhibited the immobility period in mice. Addition of yohimbine (2 mg/kg i.p.) potentiated the antidepressant action of fluoxetine or venlafaxine in mouse FST as the animals showed a decrease in the immobility period compared to the fluoxetine or venlafaxine per se group, respectively.


CONCLUSIONS
The present study not only demonstrated the association of alpha(2)-receptors in the antidepressant effect of fluoxetine or venlafaxine, but also supports its adjuvant therapy with other antidepressant drugs.
Dhir
Ashish
A
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Kulkarni
S K
SK
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D003511:Cyclohexanols / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013550:Swimming; D000069470:Venlafaxine Hydrochloride; D015016:Yohimbine / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D005473:Fluoxetine; D018341:Receptors, Adrenergic, alpha-2; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride; D015016:Yohimbine