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Aim  Cariprazine, a dopamine D 3 ‐preferring D 3 /D 2  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 ( SN c).    Methods  Extracellular recordings of individual dopaminergic neurons were performed after oral or intravenous administration of cariprazine, the D 3  receptor antagonist  SB  277011A, the D 2  receptor antagonist L741,626, and/or the D 3  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  SN c. 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  SN c, 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 D 2  receptors to cariprazine's in vivo effects is prevalent and that of D 3  receptors is less apparent.

cns neuroscience and therapeutics

The novel atypical antipsychotic cariprazine demonstrates dopamine D 2  receptor‐dependent partial agonist actions on rat mesencephalic dopamine neuronal activity