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Augmentation effect of combination therapy of aripiprazole and antidepressants on forced swimming test in mice

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Abstract

Rationale

A deficiency in brain monoamine systems (serotonin, dopamine, and/or norepinephrine) have long been hypothesized for the pathogenesis of depression. Drugs enhancing neurotransmission of those monoamines have been proven to have antidepressant effects. We hypothesized that aripiprazole, a partial D2 agonist, could increase the activity of various antidepressants in the mice forced swimming test (FST), an animal model of depression.

Objectives

The scope of this study was to investigate the antidepressant-like effect of aripiprazole, when combined with conventional antidepressants drugs.

Materials and methods

This study assessed the effects of co-administration of aripiprazole with selective serotonin reuptake inhibitors (SSRIs; sertraline, paroxetine, and citalopram), selective serotonin–norepinephrine reuptake inhibitors (SNRIs; venlafaxine and minalcipran), selective norepinephrine reuptake inhibitor (NRI; desipramine), and the dual dopamine and norepinephrine reuptake inhibitor (bupropion), using the FST in mice. Subactive doses of aripiprazole and antidepressants sertraline, paroxetine, citalopram, venlafaxine, minalcipran, bupropion (4 and 8 mg/kg), and desipramine (2 and 4 mg/kg) were given i.p. 30 and 45 min, respectively, before the test.

Results

Aripiprazole (0.03 and 0.06 mg/kg) combined with inactive doses of antidepressants, increased the activity of all antidepressants with the exception of bupropion and desipramine.

Conclusion

The augmentation effects of aripiprazole, in the present study, are in agreement with clinical evidence suggesting that aripiprazole may enhance the efficacy of therapeutic effect of SSRIs and SNRIs but not of NRI. These results suggest that augmentation effect of aripiprazole only appears when 5-HT system is activated and might implicate complex regulation between dopamine and 5-HT1A and 5-HT2A receptors.

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Abbreviations

FST:

Forced swimming test

ACTI:

Actimeter test

DA:

Dopamine

SNRI:

Selective serotonin–norepinephrine reuptake inhibitors

SSRI:

Selective serotonin reuptake inhibitors

NRI:

Selective norepinephrine reuptake inhibitor

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Authors and Affiliations

  1. EA 3256 Neurobiologie de l’anxiété et de la dépression, Faculté de Médecine 1, rue Gaston Veil, BP 53508, 44035, Nantes cedex 01, France

    Michel Bourin, Franck Chenu, Corina Prica & Martine Hascoët

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  1. Michel Bourin
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  2. Franck Chenu
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  3. Corina Prica
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  4. Martine Hascoët
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Correspondence to Michel Bourin.

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Bourin, M., Chenu, F., Prica, C. et al. Augmentation effect of combination therapy of aripiprazole and antidepressants on forced swimming test in mice. Psychopharmacology 206, 97–107 (2009). https://doi.org/10.1007/s00213-009-1583-7

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  • DOI: https://doi.org/10.1007/s00213-009-1583-7

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