, Volume 136, Issue 2, pp 190–197

Antidepressant behavioral effects by dual inhibition of monoamine reuptake in the rat forced swimming test

  • J.-P. Rénéric
  • I. Lucki

DOI: 10.1007/s002130050555

Cite this article as:
Rénéric, JP. & Lucki, I. Psychopharmacology (1998) 136: 190. doi:10.1007/s002130050555


 Because of clinical interest in the effects of antidepressant drugs that exert their effects on multiple neurotransmitter systems, the behavioral effects produced by combined treatment with an SSRI (fluoxetine) with a selective norepinephrine (NE; desipramine) or dopamine (DA) reuptake inhibitor (buproprion) were examined in the forced swimming test (FST), a behavioral test in rodents that predicts the clinical activity of antidepressants. Three additional compounds with mixed activity as NE-5-HT reuptake inhibitors, milnacipran, duloxetine and venlafaxine, were also examined. Desipramine and fluoxetine both reduced immobility in the FST, but desipramine increased only climbing behavior, whereas fluoxetine increased only swimming behavior. The combination of fluoxetine with desipramine or bupropion increased both climbing and swimming behaviors at certain doses, but higher doses of desipramine when combined with fluoxetine replaced swimming behavior with climbing behavior. The mixed NE-5-HT reuptake inhibitors milnacipran and duloxetine reduced immobility and increased climbing behavior, but did not alter swimming. Venlafaxine reduced immobility and increased swimming behavior, except at the highest dose tested (80mg/kg), which increased both swimming and climbing behaviors. Thus, combining certain doses of pharmacologically selective monoamine reuptake inhibitors, or the mixed reuptake inhibitor venlafaxine, produced a pattern of mixed active behaviors in the FST (climbing and swimming) that may reflect the activity of multiple neurotransmitters, especially the combination of enhanced 5-HT and DA activity. The combination of higher doses of desipramine with fluoxetine, or compounds with mixed activity at inhibiting NE and 5-HT reuptake, demonstrated effects similar to those of desipramine alone and may reflect inhibition of the expression of serotonergic antidepressant behavioral effects by selective NE reuptake inhibitors.

Key words Antidepressant Forced swimming Serotonin Norepinephrine Dopamine Desipramine Fluoxetine Venlafaxine Milnacipran Duloxetine Behavior 

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • J.-P. Rénéric
    • 1
  • I. Lucki
    • 1
  1. 1.Departments of Psychiatry and Pharmacology, 3600 Market Street, Room 748, University of Pennsylvania, Philadelphia, PA 19104-2648, USA Fax: +1-215-573-2149, e-mail:

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