RATIONALE: Cariprazine (RGH-188) is a D₃-preferring dopamine D₃/D₂ receptor 
partial agonist antipsychotic candidate for the treatment of schizophrenia and 
bipolar mania. Substance abuse is a frequent comorbidity of both disorders and 
is associated with serious health issues. Based on preclinical efficacy, 
dopamine D₂ and D₃ receptor partial agonists and antagonists are assumed to have 
relapse-preventing potential in human cocaine addiction.
OBJECTIVES: We investigated the anti-abuse potential of cariprazine in cocaine 
self-administration paradigms. Aripiprazole and bifeprunox were used as 
comparators because of their pharmacological similarity to cariprazine.
METHODS: The effects of compounds on cocaine's rewarding effect were 
investigated in a continuous self-administration regimen. The relapse-preventing 
potential of drugs was studied in rats with a history of cocaine 
self-administration after a period of complete abstinence in a relapse to 
cocaine-seeking paradigm.
RESULTS: Cariprazine, as well as aripiprazole and bifeprunox, were able to 
reduce the rewarding effect of cocaine (minimum effective doses were 0.17, 1, 
and 0.1 mg/kg, respectively) and attenuated relapse to cocaine seeking with half 
maximal effective dose [ED₅₀] values of 0.2, 4.2, and 0.17 mg/kg, respectively.
CONCLUSIONS: These results may predict a relapse-preventing action for 
cariprazine in humans in addition to its already established antipsychotic and 
antimanic efficacy.