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.
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22 May 2019
After publication of this paper, the authors determined an error in Fig. 3. Below is the correct Fig. 3.
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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.
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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.
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Lapointe, T., Hudson, R., Daniels, S. et al. Effects of combined escitalopram and aripiprazole in rats: role of the 5-HT1a receptor. Psychopharmacology 236, 2273–2281 (2019). https://doi.org/10.1007/s00213-019-05225-z
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DOI: https://doi.org/10.1007/s00213-019-05225-z