The novel atypical antipsychotic cariprazine demonstrates dopamine D2 receptor‐dependent partial agonist actions on rat mesencephalic dopamine neuronal activity

Autor: Bela Kiss, Charles R. Ashby, Renaud Rovera, Bence Farkas, Nika Adham, Sarah Delcourte, Nasser Haddjeri
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Male
Indoles
Patch-Clamp Techniques
Time Factors
Action Potentials
Pharmacology
Piperazines
Rats
Sprague-Dawley
chemistry.chemical_compound
0302 clinical medicine
Piperidines
Tetrahydroisoquinolines
substantia nigra pars compacta
Pharmacology (medical)
Dopaminergic
Ventral tegmental area
Substantia Nigra
Psychiatry and Mental health
medicine.anatomical_structure
Dopamine receptor
Dopamine Agonists
Original Article
medicine.drug
Agonist
medicine.drug_class
cariprazine
ventral tegmental area
Cariprazine
03 medical and health sciences
Dopamine receptor D3
Dopamine
Physiology (medical)
Dopamine receptor D2
Nitriles
Oxazines
medicine
Animals
Benzopyrans
Dose-Response Relationship
Drug
Dopaminergic Neurons
Original Articles
electrophysiology
030227 psychiatry
Rats
schizophrenia
chemistry
nervous system
030217 neurology & neurosurgery
dopamine receptors
Zdroj: CNS Neuroscience & Therapeutics
ISSN: 1755-5949
1755-5930
Popis: Aim Cariprazine, a dopamine D3 -preferring D3 /D2 receptor partial agonist, is FDA approved for the treatment of schizophrenia and acute manic or mixed episodes of bipolar disorder. This study used in vivo electrophysiological techniques in anesthetized rats to determine cariprazine's effect on dopaminergic cell activity in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Methods Extracellular recordings of individual dopaminergic neurons were performed after oral or intravenous administration of cariprazine, the D3 receptor antagonist SB 277011A, the D2 receptor antagonist L741,626, and/or the D3 receptor agonist PD 128,907. Results Acute oral treatment with cariprazine significantly increased and chronic cariprazine significantly decreased the number of spontaneously firing dopaminergic neurons in the VTA, but not in the SNc. Intravenous administration of cariprazine partially but significantly inhibited dopaminergic neuronal firing in both regions, which was prevented by L741,626 but not SB 277011A. In both VTA and SNc, cariprazine, SB 277011A, and L741,626 significantly antagonized the suppression of dopamine cell firing elicited by PD 128,907. Conclusions Cariprazine significantly modulates the number of spontaneously active VTA dopamine neurons and moderately suppresses midbrain dopamine neuronal activity. The contribution of dopamine D2 receptors to cariprazine's in vivo effects is prevalent and that of D3 receptors is less apparent.
Databáze: OpenAIRE
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