Negative symptoms and cognitive impairment associated with schizophrenia are 
strongly associated with poor functional outcome and reduced quality of life and 
remain an unmet clinical need. Cariprazine is a dopamine D3/D2 receptor partial 
agonist with preferential binding to D3 receptors, recently approved by the FDA 
for the treatment of schizophrenia and manic or mixed episodes associated with 
bipolar I disorder. The aim of this study is to evaluate effects of cariprazine 
in an animal model of cognitive deficit and negative symptoms of schizophrenia. 
Following sub-chronic PCP administration (2mg/kg, IP for 7 days followed by 7 
days drug-free), female Lister Hooded rats were administered cariprazine (0.05, 
0.1, or 0.25mg/kg, PO) or risperidone (0.16 or 0.1mg/kg, IP) before testing in 
novel object recognition (NOR), reversal learning (RL), and social interaction 
(SI) paradigms. As we have consistently demonstrated, sub-chronic PCP 
significantly impaired behavior in these tests. Deficits were significantly 
improved by cariprazine, in a dose dependent manner in the operant RL test with 
efficacy at lower doses in the NOR and SI tests. Locomotor activity was reduced 
at the highest doses of 0.1mg/kg and 0.25mg/kg in NOR and SI. Risperidone also 
reversed the PCP-induced deficit in all tests. In conclusion, cariprazine was 
effective to overcome PCP-induced deficits in cognition and social behavior in a 
thoroughly validated rat model in tests representing specific symptom domains in 
schizophrenia patients. These findings support very recent results showing 
efficacy of cariprazine in the treatment of negative symptoms in schizophrenia 
patients.