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.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Lapointe T,Hudson R,Daniels S,Melanson B,Zhou Y,Leri Fdoi
10.1007/s00213-019-05225-zsubject
Has Abstractpub_date
2019-07-01 00:00:00pages
2273-2281issue
7eissn
0033-3158issn
1432-2072pii
10.1007/s00213-019-05225-zjournal_volume
236pub_type
杂志文章abstract:RATIONALE:Cannabis (CB) use and dependence are associated with regionally specific alterations to brain circuitry and substantial psychosocial impairment. OBJECTIVES:The objective of this study was to investigate the association between CB use and dependence, and the volumes of brain regions critically involved in goa...
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