title: Effects of cariprazine, a novel antipsychotic, on cognitive deficit and negative symptoms in a rodent model of schizophrenia symptomatology.
abstract: 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.
authors.affiliation: Manchester Pharmacy School, University of Manchester, Manchester, UK. Electronic address: joanna.neill@manchester.ac.uk.
authors.forename: Jo C
authors.initials: JC
authors.lastname: Neill
authors.affiliation: Manchester Pharmacy School, University of Manchester, Manchester, UK.
authors.forename: Ben
authors.initials: B
authors.lastname: Grayson
authors.affiliation: Pharmacological and Safety Research, Gedeon Richter Plc, Budapest, Hungary.
authors.forename: Béla
authors.initials: B
authors.lastname: Kiss
authors.affiliation: Pharmacological and Safety Research, Gedeon Richter Plc, Budapest, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Gyertyán
authors.affiliation: Prescott Medical Communications Group, Chicago, IL, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Ferguson
authors.affiliation: Forest Research Institute, an Allergan Affiliate, Jersey City, NJ, USA.
authors.forename: Nika
authors.initials: N
authors.lastname: Adham
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000188:drug therapy* / Q000503:physiopathology; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D009043:Motor Activity / Q000187:drug effects; D018697:Nootropic Agents / Q000494:pharmacology; D010622:Phencyclidine; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D021641:Recognition, Psychology / Q000187:drug effects; D018967:Risperidone / Q000494:pharmacology; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D012919:Social Behavior
chemical_list: D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D018697:Nootropic Agents; D010879:Piperazines; C533287:cariprazine; D010622:Phencyclidine; D018967:Risperidone
keywords: Cariprazine; Cognition; Dopamine D(3) receptor; Negative symptoms; Phencyclidine (PCP); Schizophrenia