T-817MA, a novel neurotrophic compound, ameliorates phencyclidine-induced disruption of sensorimotor gating.

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Seo T, Sumiyoshi T, Tsunoda M, Tanaka K, Uehara T, Matsuoka T, Itoh H, Kurachi M

T-817MA, a novel neurotrophic compound, ameliorates phencyclidine-induced disruption of sensorimotor gating.

Psychopharmacology (Berl). 2008 Apr;197(3):457-64. doi: 10.1007/s00213-007-1057-8. Epub 2008 Feb 5.

PubMed ID
18251012 [ View in PubMed
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Abstract

RATIONALE: Neurodegenerative changes have been suggested to provide a basis for the pathophysiology of schizophrenia. T-817MA (1-{3-[2-(1-benzothiophen-5-yl) ethoxy] propyl} azetidin-3-ol maleate) is a novel compound with neuroprotective and neurite-outgrowth effects, as elicited in rat primary cultured neurons. OBJECTIVES: We examined the effect of T-817MA on phencyclidine (PCP)-induced disruption of prepulse inhibition (PPI), a measure of sensorimotor gating, in male Wistar rats. MATERIALS AND METHODS: In chronic experiments, male Wistar rats were injected intermittently with PCP (2.0 mg/kg, i.p., three times per week) or vehicle (saline, 2.0 ml/kg) for 1 month. T-817MA (0.21 or 0.07 mg/ml, p.o.) or distilled water was administered throughout the study period. In an acute experiment, T-817MA (8.4 mg/kg, p.o.) or distilled water was administered, followed by treatment with PCP (2.0 mg/kg, i.p.) or vehicle (saline, 2.0 ml/kg), before PPI measurements. RESULTS: Intermittent administration of PCP for 1 month induced persistent disruption of PPI. Coadministration of T-817MA at 0.21 mg/ml but not 0.07 mg/ml completely blocked PCP-induced disruption of PPI, whereas T-817MA (0.21 mg/ml) by itself did not show a significant effect on PPI in control rats. On the other hand, single administration of T-817MA did not affect PPI disruption by acute treatment with PCP. CONCLUSIONS: These results suggest that T-817MA is effective in ameliorating sensorimotor gating deficits caused by chronic PCP treatment, possibly via neuroprotective actions. Our findings provide a novel therapeutic approach for patients with schizophrenia.

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