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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. 34:1143-1154
- Publication Year :
- 2020
- Publisher :
- SAGE Publications, 2020.
-
Abstract
- Background: 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). Aims: 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. Methods: 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. Results: 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. Conclusion: 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.
- Subjects :
- Pharmacology
medicine.medical_specialty
business.industry
Hippocampus
Cariprazine
Neurotransmission
Partial agonist
030227 psychiatry
03 medical and health sciences
Psychiatry and Mental health
chemistry.chemical_compound
0302 clinical medicine
Endocrinology
Monoamine neurotransmitter
chemistry
Dopamine
Internal medicine
Medicine
Locus coeruleus
Pharmacology (medical)
Serotonin
business
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 14617285 and 02698811
- Volume :
- 34
- Database :
- OpenAIRE
- Journal :
- Journal of Psychopharmacology
- Accession number :
- edsair.doi...........fb47dcf3042e31f2b0c72680b7d5b23c