Psychopharmacology

, Volume 138, Issue 1, pp 1–8

Dose-dependent noradrenergic and serotonergic properties of venlafaxine in animal models indicative of antidepressant activity

Authors

  • J. P. Redrobe
    • GIS Médicament, JE 2027 Neurobiologie de l’anxieté, Faculté de Médecine BP 53508, 1 rue Gaston Veil, F-44035 Nantes Cedex, France Fax: + 33-2-40412856
  • M. Bourin
    • GIS Médicament, JE 2027 Neurobiologie de l’anxieté, Faculté de Médecine BP 53508, 1 rue Gaston Veil, F-44035 Nantes Cedex, France Fax: + 33-2-40412856
  • M. C. Colombel
    • GIS Médicament, JE 2027 Neurobiologie de l’anxieté, Faculté de Médecine BP 53508, 1 rue Gaston Veil, F-44035 Nantes Cedex, France Fax: + 33-2-40412856
  • G. B. Baker
    • GIS Médicament, JE 2027 Neurobiologie de l’anxieté, Faculté de Médecine BP 53508, 1 rue Gaston Veil, F-44035 Nantes Cedex, France Fax: + 33-2-40412856
ORIGINAL INVESTIGATION

DOI: 10.1007/s002130050638

Cite this article as:
Redrobe, J., Bourin, M., Colombel, M. et al. Psychopharmacology (1998) 138: 1. doi:10.1007/s002130050638

Abstract

The present study was undertaken to investigate thoroughly the preclinical psychopharmacological profile of venlafaxine, testing a wide range of doses in animal models indicative of antidepressant-like effects. Venlafaxine was found to be active in mouse forced swimming test (at 8, 16, 32 and 64 mg/kg) and to increase spontaneous locomotor activity (at 16, 32 and 64 mg/kg). Venlafaxine antagonised apomorphine-induced (16 mg/kg) hypothermia (at 2, 4, 8, 16, 32 and 64 mg/kg). Pretreatment with PCPA significantly attenuated the anti-immobility effects of venlafaxine (8 and 16 mg/kg; P < 0.01) in the mouse forced swimming test. Venlafaxine at a dose of 32 mg/kg remained active, despite PCPA pretreatment. DSP-4 significantly attenuated the anti-immobility effects of venlafaxine (16 mg/kg; P < 0.05), whereas venlafaxine at 32 mg/kg remained active, despite DSP-4 pretreatment. Venlafaxine was active in the forced swimming test when administered at sub-effective doses in combination with (±) pindolol (venlafaxine: 1 and 2 mg/kg), RU 24969 (venlafaxine: 1, 2 and 4 mg/kg), 8-OH-DPAT (venlafaxine: 4 mg/kg), clonidine (venlafaxine: 1, 2 and 4 mg/kg), lithium (venlafaxine: 1, 2, and 4 mg/kg) and quinine (venlafaxine: 1 and 2 mg/kg). Prior administration with NAN-190 antagonised the anti-immobility effects of venlafaxine (8, 16 and 32 mg/kg). Interaction studies did not induce changes in locomotor activity. The results of the present study indicated that, at low doses, venlafaxine inhibited serotonin reuptake, while at higher doses it inhibited both serotonin and noradrenaline reuptake.

Key words VenlafaxineNoradrenalineSerotoninAnimal model of depression

Copyright information

© Springer-Verlag Berlin Heidelberg 1998