Psychopharmacology · 2019
Effects of combined escitalopram and aripiprazole in rats: role of the 5-HT1a receptor.
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Lapointe Thomas, Hudson Roger, Daniels Stephen, Melanson Brett, Zhou Yan, Leri Francesco
Аннотация
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.
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.