Antipsychotic-like profile of CIQ isomers in animal models of schizophrenia

Behav Pharmacol. 2020 Sep;31(6):524-534. doi: 10.1097/FBP.0000000000000532.

Abstract

Earlier, we have shown the efficacy of racemic (±) CIQ, a positive allosteric modulator of GluN2C/2D receptor against MK-801 induced impairment of prepulse inhibition as well as working memory. The present study investigated the antipsychotic-like profile of different CIQ (±, +, -) isomers against schizophrenia-like symptoms in series of behavioural animal models like apomorphine climbing, social isolation behaviour and NMDA receptor antagonist MK-801 induced cognitive deficits. Further, we also tested CIQ (±, +, -) isomers in neurodevelopmental model against MK-801induced deficits using open field test, Y-maze test and novel object recognition test. CIQ (±, +, -) isomers decreased climbing behaviour, increased social interaction and improved the MK-801 induced deficits in working memory in Y-maze. Further, CIQ (±, +) but not CIQ (-) improved the recognition memory in novel object recognition test as well as reduced hyperlocomotion and stereotyped behaviour. We conclude that CIQ (±, +) but not CIQ (-) exhibit the significant antipsychotic-like profile.

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Apomorphine / pharmacology
  • Disease Models, Animal
  • Dizocilpine Maleate / pharmacology
  • Male
  • Maze Learning
  • Mice
  • Receptors, N-Methyl-D-Aspartate / drug effects*
  • Schizophrenia / drug therapy*
  • Social Interaction / drug effects
  • Stereoisomerism
  • Stereotyped Behavior / drug effects

Substances

  • Antipsychotic Agents
  • NR2C NMDA receptor
  • NR2D NMDA receptor
  • Receptors, N-Methyl-D-Aspartate
  • Dizocilpine Maleate
  • Apomorphine