Attenuation of anhedonia by cariprazine in the chronic mild stress model of depression

作者：Papp Mariusz; Gruca Piotr; Lason Tyburkiewicz Magdalena; Adham Nika; Kiss Bela; Gyertyan Istvan

来源：Behavioural Pharmacology, 2014, 25(5-6): 567-574.

DOI：10.1097/FBP.0000000000000070

• anhedonia
• antipsychotic agents
• bipolar disorder
• cariprazine
• chronic mild stress
• depression
• dopamine D-3 receptor
• dopamine receptor partial agonist
• negative symptoms
• schizophrenia

The aim of this study was to evaluate whether chronic treatment with cariprazine, a dopamine D-2 and D-3 receptor partial agonist with preferential binding to D-3 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.

• 出版日期2014-9