title: LASSBio-579, a prototype antipsychotic drug, and clozapine are effective in novel object recognition task, a recognition memory model.
abstract: Previous studies on the N-phenylpiperazine derivative LASSBio-579 have suggested that LASSBio-579 has an atypical antipsychotic profile. It binds to D2, D4 and 5-HT1A receptors and is effective in animal models of schizophrenia symptoms (prepulse inhibition disruption, apomorphine-induced climbing and amphetamine-induced stereotypy). In the current study, we evaluated the effect of LASSBio-579, clozapine (atypical antipsychotic) and haloperidol (typical antipsychotic) in the novel object recognition task, a recognition memory model with translational value. Haloperidol (0.01 mg/kg, orally) impaired the ability of the animals (CF1 mice) to recognize the novel object on short-term and long-term memory tasks, whereas LASSBio-579 (5 mg/kg, orally) and clozapine (1 mg/kg, orally) did not. In another set of experiments, animals previously treated with ketamine (10 mg/kg, intraperitoneally) or vehicle (saline 1 ml/100 g, intraperitoneally) received LASSBio-579, clozapine or haloperidol at different time-points: 1 h before training (encoding/consolidation); immediately after training (consolidation); or 1 h before long-term memory testing (retrieval). LASSBio-579 and clozapine protected against the long-term memory impairment induced by ketamine when administered at the stages of encoding, consolidation and retrieval of memory. These findings point to the potential of LASSBio-579 for treating cognitive symptoms of schizophrenia and other disorders.
authors.affiliation: aPost Graduate Program in Pharmaceutical Sciences, Department of Raw Material Production, Federal University of Rio Grande do Sul, Porto Alegre bLaboratory of Evaluation and Synthesis of Bioactive substances, Department of Pharmaceuticals, Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Camila B
authors.initials: CB
authors.lastname: Antonio
authors.forename: Andresa H
authors.initials: AH
authors.lastname: Betti
authors.forename: Vivian
authors.initials: V
authors.lastname: Herzfeldt
authors.forename: Eliezer J
authors.initials: EJ
authors.lastname: Barreiro
authors.forename: Carlos A M
authors.initials: CA
authors.lastname: Fraga
authors.forename: Stela M K
authors.initials: SM
authors.lastname: Rates
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology; D004195:Disease Models, Animal; D006220:Haloperidol / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D057567:Memory, Long-Term / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects; D051379:Mice; D010879:Piperazines / Q000494:pharmacology*; D021641:Recognition, Psychology / Q000187:drug effects*; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; C518328:LASSBio-579; D010879:Piperazines; D007649:Ketamine; D003024:Clozapine; D006220:Haloperidol