How Scientists Synergize Antidepressant Effectiveness To Leverage Improved Depression Treatment

In this inaugural release of First-Person Science, Roger Hudson speaks with Thomas Lapointe about his recently published manuscript that explores the behavioural and brain mRNA effects of combined escitalopram (an SSRI; antidepressant) and adjunct aripiprazole (5-HT1a agonist) in rats, with a specific focus on the 5-HT1a receptor. This podcast also discusses how scientists are enhancing the therapeutic efficacy of antidepressants and some of the mechanisms involved.

"Effects of combined escitalopram and aripiprazole in rats: role of the 5-HT1a receptor", published in Psychopharmacology [2019 Jul;236(7):2273-2281] / DOI:10.1007/s00213-019-05225-z.
https://link.springer.com/article/10.1007/s00213-019-05225-z

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

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First-Person Science is the first and only Webcast dedicated to in-depth exploration of scientific research articles w/ first-hand perspectives & narratives from the authors themselves. We aim to increase promotion of neuroscience research articles and provide exposure for the scientists behind the work, as well as enhance public accessibility to publicly-funded, cutting-edge research.

Hosted/Produced by Roger Hudson & Thomas Lapointe