LASSBio-579, a prototype antipsychotic drug, and clozapine are effective in novel object recognition task, a recognition memory model

Behav Pharmacol. 2016 Jun;27(4):339-49. doi: 10.1097/FBP.0000000000000200.

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Clozapine / pharmacology
  • Disease Models, Animal
  • Haloperidol / pharmacology
  • Ketamine / pharmacology
  • Male
  • Memory, Long-Term / drug effects
  • Memory, Short-Term / drug effects
  • Mice
  • Piperazines / pharmacology*
  • Recognition, Psychology / drug effects*
  • Schizophrenia / drug therapy*
  • Schizophrenia / physiopathology
  • Time Factors

Substances

  • Antipsychotic Agents
  • LASSBio-579
  • Piperazines
  • Ketamine
  • Clozapine
  • Haloperidol