The aim of this study was to evaluate whether chronic treatment with 
cariprazine, a dopamine D2 and D3 receptor partial agonist with preferential 
binding to D3 receptors, shows antidepressant-like effects in the chronic mild 
stress (CMS)-induced anhedonia model. Male Wistar rats were subjected to the CMS 
procedure for 7 weeks; nonstressed animals served as controls. For the last 5 
weeks of the CMS procedure, rats were injected once daily with vehicle, 
imipramine (10 mg/kg), aripiprazole (1 and 5 mg/kg), or cariprazine (0.01, 0.03, 
0.065, 0.25, and 1.0 mg/kg). Activity in reversing CMS-induced decreases in 
consumption of 1% solution of sucrose was measured. CMS significantly reduced 
sucrose intake. Imipramine, and both doses of aripiprazole and cariprazine 0.03, 
0.065, and 0.25 mg/kg significantly attenuated CMS-induced reductions in sucrose 
intake; the lowest and highest cariprazine doses (0.01 and 1 mg/kg) did not have 
this effect. Cariprazine showed greater potency (ED50=0.052) relative to 
aripiprazole (ED50=4.4) in this model. Thus, in the rat CMS model, cariprazine 
showed antidepressant-like action with greater potency than aripiprazole. These 
results suggest that cariprazine may have clinical utility in the treatment of 
depression and the negative symptoms of schizophrenia.