STOP knockout and NMDA NR1 hypomorphic mice exhibit deficits in sensorimotor gating

Behav Brain Res. 2005 Sep 8;163(2):257-64. doi: 10.1016/j.bbr.2005.05.012.

Abstract

Schizophrenia is a chronic and debilitating disease which is thought to arise from a neuro-developmental disorder. Both the stable tubule-only polypeptide (STOP) protein and the N-methyl-D-aspartate (NMDA) NR1 subunit are involved in neuronal development and physiology. It has therefore been postulated that transgenic mice lacking either the STOP or the NMDAR1 gene would show a 'schizophrenic-like' phenotype. Here, STOP knockout and NMDA NR1 hypomorphic mice were assessed in a behavioural measure that can be used to detect schizophrenic-like phenotypes: a change in sensorimotor gating, measured through prepulse inhibition (PPI). STOP knockout mice were further assessed in another measure of 'schizophrenic-like behaviour': hyperlocomotion. The PPI deficit exhibited by both the STOP knockout and NMDA knockdown mice could not be reversed by acute treatment with the atyptical antipsychotic, clozapine (1 mg/kg, i.p.) but the hyperlocomotion shown by the STOP knockout mice was reversed with the same acute dose of clozapine.

Publication types

  • Comparative Study

MeSH terms

  • Acoustic Stimulation / methods
  • Animals
  • Antipsychotic Agents / administration & dosage
  • Body Temperature / drug effects
  • Body Temperature / genetics
  • Body Weight / drug effects
  • Body Weight / genetics
  • Clozapine / administration & dosage
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Drug Interactions
  • Enzyme Inhibitors / pharmacology
  • Gait Disorders, Neurologic / drug therapy
  • Gait Disorders, Neurologic / genetics*
  • Gait Disorders, Neurologic / physiopathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microtubule-Associated Proteins / deficiency*
  • Motor Activity / drug effects
  • Motor Activity / genetics
  • Neural Inhibition / drug effects
  • Neural Inhibition / genetics
  • Phencyclidine / pharmacology
  • Receptors, N-Methyl-D-Aspartate / deficiency*
  • Reflex, Acoustic / drug effects
  • Reflex, Acoustic / genetics
  • Rotarod Performance Test / methods
  • Somatosensory Cortex / drug effects
  • Somatosensory Cortex / physiopathology*
  • Swimming
  • Time Factors

Substances

  • Antipsychotic Agents
  • Enzyme Inhibitors
  • Microtubule-Associated Proteins
  • Mtap6 protein, mouse
  • NR1 NMDA receptor
  • Receptors, N-Methyl-D-Aspartate
  • Phencyclidine
  • Clozapine