Effect of Addition of Yohimbine (Alpha-2-Receptor Antagonist) to the Antidepressant Activity of Fluoxetine or Venlafaxine in the Mouse Forced Swim Test

Vol. 80, No. 4, 2007

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Effect of Addition of Yohimbine (Alpha-2-Receptor Antagonist) to the Antidepressant Activity of Fluoxetine or Venlafaxine in the Mouse Forced Swim Test
Ashish Dhir, S.K. Kulkarni

Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India

Address of Corresponding Author

Pharmacology 2007;80:239-243 (DOI: 10.1159/000104877)

Key Words

Venlafaxine
Fluoxetine
Yohimbine
Forced swim test

Abstract

Background/Aims: 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. Method: 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. Conclusion: 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.

Author Contacts

Prof. S.K. Kulkarni
Pharmacology Division, University Institute of Pharmaceutical Sciences
Panjab University
Chandigarh 160014 (India)
Tel. +91 172 253 4114 or 254 1142, Fax +91 172 254 1142, E-Mail skpu@yahoo.com

Article Information

Received: February 9, 2007
Accepted: February 15, 2007
Published online: July 6, 2007
Number of Print Pages : 5
Number of Figures : 2, Number of Tables : 1, Number of References : 25

Medline Abstract (ID 17622775)

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