title: T-817MA, but Not Haloperidol and Risperidone, Restores Parvalbumin-Positive γ -Aminobutyric Acid Neurons in the Prefrontal Cortex and Hippocampus of Rats Transiently Exposed to MK-801 at the Neonatal Period.
abstract: The number of parvalbumin (PV)-positive γ -aminobutyric acid (GABA) neurons is decreased in the brain of rats transiently exposed to MK-801, an N-methyl-D-aspartate (NMDA) receptor blocker, in the neonatal stage (Uehara et al. (2012)). T-817MA [1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl} azetidin-3-ol maleate] is a neuroprotective agent synthesized for the treatment of psychiatric disorders characterized by cognitive disturbances, such as dementia. We herein sought to determine whether T-817MA, haloperidol (HPD), or risperidone (RPD) would ameliorate the decrease in the number of PV-positive GABA neurons in the medial prefrontal cortex (mPFC) and hippocampus of the model animals. Rats were treated with MK-801 (0.2 mg/kg/day) or vehicle on postnatal days (PD) 7-10, and the number of PV-positive neurons in the mPFC and hippocampus were measured on PDs 63. T-817MA (20 mg/kg), HPD (1 mg/kg), or RPD (1 mg/kg) were administered during PDs 49-62. Fourteen-day administration of T-817MA reversed the decrease in the number of PV-positive neurons in the above brain regions of rats given MK-801, whereas HPD and RPD were ineffective. These results indicate that T-817MA provides a novel pharmacologic strategy to enhance cognitive function in patients with schizophrenia.
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan ; Division of Molecular and Clinical Neurobiology, Department of Psychiatry, Ludwig-Maximilians University of Munich, Nußbaumstraße 7, 80336 Munich, Germany.
authors.forename: Takashi
authors.initials: T
authors.lastname: Uehara
authors.forename: Tomiki
authors.initials: T
authors.lastname: Sumiyoshi
authors.forename: Tomonori
authors.initials: T
authors.lastname: Seo
authors.forename: Tadasu
authors.initials: T
authors.lastname: Matsuoka
authors.forename: Hiroko
authors.initials: H
authors.lastname: Itoh
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kurachi