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

Papp, Mariusza; Gruca, Piotra; Lasoń-Tyburkiewicz, Magdalenaa; Adham, Nikab; Kiss, Bélac; Gyertyán, Istvánc

doi: 10.1097/FBP.0000000000000070
Research Reports

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.

aBehavioural Pharmacology Laboratory, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland

bDepartment of Pharmacology, Forest Research Institute, Jersey City, New Jersey, USA

cDivision of Pharmacology,Gedeon Richter Plc, Budapest, Hungary

Correspondence to István Gyertyán, PhD, Gedeon Richter Plc, H-1103 Budapest 10, Gyomroi u. 19-21, Hungary E-mail: i.gyertyá

Received April 1, 2014

Accepted June 23, 2014

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins