Long-term administration of cariprazine increases locus coeruleus noradrenergic neurons activity and serotonin1A receptor neurotransmission in the hippocampus.

Journal of Psychopharmacology
Mostafa El MansariPierre Blier

Abstract

Cariprazine, the novel dopamine (DA) D3-preferring D3/D2 and serotonin (5-HT)1A receptor partial agonist, has activity as an adjunctive therapy in major depressive disorder (MDD). This study aims to investigate the effects of chronic cariprazine administration in combination with the selective serotonin reuptake inhibitor escitalopram on the activity of monoaminergic systems. Rats received cariprazine alone and in adjunct to escitalopram for 2 and 14 days and the firing activity of dorsal raphe nucleus 5-HT, locus coeruleus norepinephrine (NE) and ventral tegmental area DA neurons was assessed. 5-HT and NE neurotransmission in hippocampus pyramidal neurons was evaluated by assessing tonic activation of their 5-HT1A, and α1- and α2-adrenergic receptors, using their selective antagonists. Two and 14-day cariprazine regimens increased the firing rate of NE, but not 5-HT and DA neurons. Addition of cariprazine to escitalopram reversed the inhibitory effect of escitalopram on NE but not 5-HT and DA neurons. In the hippocampus, there was an increase in neurotransmission at 5-HT1A receptors in cariprazine-treated rats, but no change in overall NE transmission by either regimen. Cariprazine increased NE neuronal firing and reversed the...Continue Reading

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