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Long-term administration of cariprazine increases locus coeruleus noradrenergic neurons activity and serotonin1A receptor neurotransmission in the hippocampus.
- Source :
-
Journal of Psychopharmacology . Oct2020, Vol. 34 Issue 10, p1143-1154. 12p. - Publication Year :
- 2020
-
Abstract
- <bold>Background: </bold>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).<bold>Aims: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>Cariprazine increased NE neuronal firing and reversed the escitalopram-induced inhibition of these neurons. Despite a lack of effect on 5-HT neuronal firing activity, there was an increase in tonic activation of hippocampus 5-HT1A receptors by cariprazine alone but not with the combination. These effects provide a possible rationale for the clinical efficacy of cariprazine as an adjunctive strategy in patients with MDD. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 02698811
- Volume :
- 34
- Issue :
- 10
- Database :
- Academic Search Index
- Journal :
- Journal of Psychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 146204525
- Full Text :
- https://doi.org/10.1177/0269881120936891