Sensorimotor Gating Deficits and Effects of Antipsychotics on the Hyperactivity in VGF-overexpressing Mice.

BACKGROUND:VGF nerve growth factor inducible (VGF) is a neuropeptide which is expressed in neuronal cells and endocrine cells. VGF is induced by several neurotrophic factors. The expression level of VGF in patients with schizophrenia is increased in cerebrospinal fluid (CSF) and prefrontal cortex. In our previous study, we generated mice in which the expression level of VGF in the brain was increased. VGF-overexpressing mice exhibited abnormal behaviors including hyperactivity. However, it remains unknown whether VGF-overexpressing mice exhibit the endophenotype of schizophrenia and whether abnormal behaviors in these mice can be improved by antipsychotics.METHODS:In the present study, we investigated schizophrenia-like behaviors and the responsiveness to antipsychotics in transgenic mice.RESULTS:VGF-overexpressing mice (1) exhibited prepulse inhibition (PPI) impairment, (2) showed normalized hyperactivity following antipsychotic drug treatment, and (3) showed abnormal responsiveness to haloperidol.CONCLUSION:Upregulation of VGF may be implicated in the pathophysiology of schizophrenia and abnormalities of dopaminergic signaling.