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Electrophysiological studies in the rat brain on the basis for aripiprazole augmentation of antidepressants in major depressive disorder

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Abstract

Rationale

Aripiprazole (ARI) is an atypical antipsychotic approved by the Food and Drug Administration for use in major depressive disorder as an adjunct to antidepressants. However, the precise mechanisms responsible for the effectiveness of ARI augmentation are not fully understood.

Objectives

The current study was aimed at examining the effects of ARI administration alone and in combination with the selective serotonin reuptake inhibitors (SSRI) escitalopram (ESC) on the firing of serotonin (5-HT), norepinephrine (NE), and dopamine (DA) neurons.

Methods

Electrophysiological experiments were carried out in anesthetized Sprague–Dawley rats. ESC was delivered via subcutaneously implanted osmotic minipumps at a dose of 10 mg/kg/day. ARI was subcutaneously injected daily at a dose of 2 mg/kg/day. Both drugs were administered for 2 and 14 days alone and in combination. Control rats received physiological saline in analogous regimens.

Results

Two-day ESC administration resulted in a significant decrease in the firing rate of 5-HT, NE, and DA neurons. Following 14 days of ESC administration, 5-HT firing returned to the baseline. The firing rate of NE and DA neurons remained significantly decreased. ARI administered for 2 or 14 days significantly increased the firing rate of 5-HT neurons by 36% and 48%, respectively, but not those of DA and NE neurons. Desensitization of somatodendritic 5-HT autoreceptors was observed after 2 days of ARI administration. The combination of the two drugs reversed the inhibitory action of ESC on the firing rate of 5-HT, NE, and DA neurons.

Conclusion

The present study showed that addition of ARI to an SSRI regimen reverses the inhibitory action of the SSRI on monoaminergic neuronal firing.

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Acknowledgements

This research was supported by Bristol-Myers Squibb. PB received a Canada Research Chair in Psychopharmacology and an Endowed Chair from the University of Ottawa, Institute of Mental Health Research. We thank Lundbeck and Janssen for supplying ESC and PALI, respectively.

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  1. Institute of Mental Health Research, University of Ottawa, 1145 Carling Avenue, Ottawa, ON, K1Z 7K4, Canada

    Olga Chernoloz, Mostafa El Mansari & Pierre Blier

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  1. Olga Chernoloz
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  2. Mostafa El Mansari
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  3. Pierre Blier
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Correspondence to Olga Chernoloz.

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Chernoloz, O., El Mansari, M. & Blier, P. Electrophysiological studies in the rat brain on the basis for aripiprazole augmentation of antidepressants in major depressive disorder. Psychopharmacology 206, 335–344 (2009). https://doi.org/10.1007/s00213-009-1611-7

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  • DOI: https://doi.org/10.1007/s00213-009-1611-7

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