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

• Published in: Behavioural brain research Vol. 163; no. 2; pp. 257 - 264
• Main Authors: Fradley, Rosa L., O’Meara, Gillian F., Newman, Richard J., Andrieux, Annie, Job, Didier, Reynolds, David S.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 08.09.2005; Elsevier Science; Elsevier
• Subjects: Acoustic Stimulation; Acoustic Stimulation - methods; Adult and adolescent clinical studies; Animals; Antipsychotic Agents; Antipsychotic Agents - administration & dosage; Behavioral psychophysiology; Biological and medical sciences; Body Temperature; Body Temperature - drug effects; Body Temperature - genetics; Body Weight; Body Weight - drug effects; Body Weight - genetics; Clozapine; Clozapine - administration & dosage; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Drug Interactions; Enzyme Inhibitors; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Gait Disorders, Neurologic; Gait Disorders, Neurologic - drug therapy; Gait Disorders, Neurologic - genetics; Gait Disorders, Neurologic - physiopathology; Hyperlocomotion; Life Sciences; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Microtubule-Associated Proteins; Microtubule-Associated Proteins - deficiency; Motor Activity; Motor Activity - drug effects; Motor Activity - genetics; Neural Inhibition; Neural Inhibition - drug effects; Neural Inhibition - genetics; Neuro-developmental disorder; Neurons and Cognition; Neurotransmission and behavior; NMDA NR1 hypomorphic mice; Phencyclidine; Phencyclidine - pharmacology; PPI; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Psychoses; Receptors, N-Methyl-D-Aspartate; Receptors, N-Methyl-D-Aspartate - deficiency; Reflex, Acoustic; Reflex, Acoustic - drug effects; Reflex, Acoustic - genetics; Rotarod Performance Test; Rotarod Performance Test - methods; Schizophrenia; Sensorimotor-gating; Somatosensory Cortex; Somatosensory Cortex - drug effects; Somatosensory Cortex - physiopathology; STOP KO mice; Swimming; Time Factors; Neuro-developmental disorder; STOP KO mice; Schizophrenia; PPI; NMDA NR1 hypomorphic mice; Sensorimotor-gating; Hyperlocomotion; Animal model; Targeting; Rodentia; Developmental disorder; Psychosis; Vertebrata; Mammalia; Gene; Mouse; Animal; NMDA; Mutation; Gating
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2005.05.012

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.