Augmentation effect of combination therapy of aripiprazole and antidepressants on forced swimming test in mice.
BACKGROUND
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 D(2) agonist, could increase the activity of various antidepressants in the mice forced swimming test (FST), an animal model of depression.


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


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.


CONCLUSIONS
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-HT(1A) and 5-HT(2A) receptors.
Bourin
Michel
M
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@univ-nantes.fr
Chenu
Franck
F
Prica
Corina
C
Hascoët
Martine
M
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000068180:Aripiprazole; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D008297:Male; D051379:Mice; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D015363:Quinolones / Q000494:pharmacology* / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D013315:Stress, Psychological / Q000188:drug therapy*
D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D000068180:Aripiprazole; D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; D015363:Quinolones; D017367:Selective Serotonin Reuptake Inhibitors