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Psychopharmacology

, Volume 236, Issue 7, pp 2273–2281 | Cite as

Effects of combined escitalopram and aripiprazole in rats: role of the 5-HT1a receptor

  • Thomas Lapointe
  • Roger Hudson
  • Stephen Daniels
  • Brett Melanson
  • Yan Zhou
  • Francesco LeriEmail author
Original Investigation
  • 248 Downloads

Abstract

Rationale

Pre-clinical and clinical studies have suggested that the antidepressant efficacy of escitalopram (ESC) can be augmented by co-administration of aripiprazole (ARI).

Objective

To establish if the effects of ESC + ARI can be altered by modulating the 5-HT1a receptor.

Methods

Sprague-Dawley male rats received ESC + ARI (10 and 2 mg/kg/day, respectively, via osmotic or by cumulative injections), as well as the 5-HT1a antagonist WAY-100635 (WAY; 0.01–1 mg/kg) and the 5-HT1a agonist 8-OH-DPAT (DPAT; 0.3–1 mg/kg) prior to testing in locomotion chambers and in the forced swim test (FST). Expression of the 5-HT1a receptor mRNA in the dorsal raphe nucleus, hippocampus, septum, and entorhinal cortex was also assessed.

Results

WAY generally synergized, while DPAT antagonized, the effect of ESC + ARI on motor activity. All groups showed significantly lower 5-HT1a mRNA in the dorsal raphe nucleus. In the hippocampus, ESC + ARI and WAY + ESC + ARI groups displayed equivalent elevations of 5-HT1a mRNA, but this was not observed in groups that received DPAT + ESC + ARI. Finally, the addition of ARI to ESC augmented the effect that ESC alone had on reducing immobility in the FST. Importantly, WAY antagonized this effect, while DPAT had no consequences.

Conclusions

Taken together, these results in rats indicate that the 5-HT1a receptor is involved in the behavioral and brain region-specific mRNA effects of ESC + ARI.

Keywords

Escitalopram Aripiprazole 5-HT1a receptor mRNA Psychomotor Forced swim Augmentation Antidepressant SSRI Depression 

Notes

Funding

This study was part of the Canadian Biomarker Integration Network in Depression (CAN-BIND) program (www.canbind.ca). CAN-BIND is an Integrated Discovery Program carried out in partnership with, and financial support from, the Ontario Brain Institute, an independent non-profit corporation, funded partially by the Ontario government. The opinions, results, and conclusions are those of the authors and no endorsement by the Ontario Brain Institute is intended or should be inferred.

Compliance with ethical standards

All experiments were approved by the Animal Care Committee of the University of Guelph and were carried out in accordance with recommendations provided by the Canadian Council on Animal Care.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Psychology, Neuroscience SpecializationUniversity of GuelphGuelphCanada
  2. 2.Laboratory of Addictive DiseasesRockefeller UniversityNew YorkUSA

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