T-817MA, a novel neurotrophic agent, ameliorates loss of GABAergic parvalbumin-positive neurons and sensorimotor gating deficits in rats transiently exposed to MK-801 in the neonatal period. 
T-817MA [1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl}azetidin-3-ol maleate] is a newly synthesized neuroprotective agent for the treatment of psychiatric disorders characterized by cognitive disturbances, such as Alzheimer's disease.  Cognitive impairment has also been suggested to be a cardinal feature of schizophrenia.  We sought to determine whether T-817MA would ameliorate sensorimotor gating deficits and loss of parvalbumin (PV)-positive γ-aminobutyric acid (GABA) neurons in the brain of rats transiently exposed to MK-801, an N-methyl-d-aspartate receptor blocker, in the neonatal stage, as an animal model of schizophrenia.  Prepulse inhibition (PPI) was examined in rats treated neonatally with MK-801 (postnatal day; PD 7-10, 0.2 mg/kg/day, s.c.)  or vehicle at PD 35 and PD 63.  The number of PV-positive GABAergic neurons in the medial prefrontal cortex (mPFC) and the hippocampus was measured after the behavioral assessments.  T-817MA (10 or 20 mg/kg) or vehicle was administered for 14 days (on PD 49-62).  Administration of T-817MA at 20 mg/kg, but not 10 mg/kg, ameliorated PPI deficits and completely reversed the decrease in the number of PV-positive GABAergic neurons in rats given MK-801.  These results indicate that T-817MA may provide a novel therapeutic approach for the treatment of cognitive deficits of schizophrenia.