Neuronal development of the hyperdopaminergic animal model

Dopamine transporter knockout (DAT KO) mice exhibited hyperdopaminergic tone in the nucleus accumbens and striatum, whereas they showed normal levels of extracellular dopamine in the prefrontal cortex. DAT KO mice showed numerous behavioral alterations that can be linked to abnormal dopaminergic function, including hyperlocomotion, deficits of prepulse inhibition (PPI) and impairment of working memory. PPI deficits were also shown in schizophrenic patients and hyperlocomotion was observed in AD/HD patients; therefore DAT KO mice had face validity for these psychiatric disorders. Impairment of neuronal development such as brain volume loss and decrease in spine density was reported especially in the prefrontal cortex of schizophrenia and AD/HD patients. We therefore investigated the neuronal development of DAT KO mice. Our results indicated that DAT KO mice had deficits of neuronal development in the prefrontal cortex similar to schizophrenia and AD/HD patients at least in part. These findings suggest that DAT KO mice are one of the useful models to investigate the impairment of neuronal development observed in psychiatric disorders including schizophrenia and AD/HD.