title: Attenuation of anhedonia by cariprazine in the chronic mild stress model of depression.
abstract: 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.
authors.affiliation: 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.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Papp
authors.forename: Piotr
authors.initials: P
authors.lastname: Gruca
authors.forename: Magdalena
authors.initials: M
authors.lastname: Lasoń-Tyburkiewicz
authors.forename: Nika
authors.initials: N
authors.lastname: Adham
authors.forename: Béla
authors.initials: B
authors.lastname: Kiss
authors.forename: István
authors.initials: I
authors.lastname: Gyertyán
mesh_terms: D059445:Anhedonia / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D000068180:Aripiprazole; D002908:Chronic Disease; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D019422:Dietary Sucrose / Q000008:administration & dosage; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects / Q000502:physiology; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000503:physiopathology*
chemical_list: D000928:Antidepressive Agents; D019422:Dietary Sucrose; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole; C533287:cariprazine; D007099:Imipramine