Journal
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
Volume 110, Issue -, Pages 98-103Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbb.2013.06.005
Keywords
Antipsychotic drug; Epoxyeicosatrienoic acids; Phencyclidine; Prepulse inhibition; Soluble epoxide hydrolase
Funding
- Intramural Research Grant for Neurological and Psychiatric Disorders of NCNP, Japan [25-1]
- Grants-in-Aid for Scientific Research [24659143] Funding Source: KAKEN
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Accumulating evidence suggests that soluble epoxide hydrolase (sEH) plays a key role in controlling levels of lipid signaling molecules, and that the potent sEH inhibitors may be potential therapeutic drugs for a number of diseases associated with metabolism of epoxyeicosatrienoic acids (EETs). This study was undertaken to examine whether the potent sEH inhibitor AS2586114 could attenuate behavioral abnormalities (e.g., hyperlocomotion and prepulse inhibition (PPI) deficits) in male ddY mice after a single administration of the N-methyl-D-aspartate (NMDA) receptor antagonist phencyclidine (PCP). A single oral administration of AS2586114 (10, 30, or 100 mg/kg) attenuated the hyperlocomotion in mice after the administration of PCP (3.0 mg/kg, s.c), in a dose dependent manner. Furthermore, a single oral administration of AS2586114 (10, 30, or 100 mg/kg) improved the PPI deficits in mice after the administration of PCP (3.0 mg/kg, s.c), in a dose dependent manner. In addition, the atypical antipsychotic drug clozapine (10 mg/kg, p.o.) significantly attenuated hyperlocomotion and PPI deficits after the administration of PCP (3.0 mg/kg, s.c.). In conclusion, this study suggests that A52586114 may have antipsychotic activity in PCP models of schizophrenia. Therefore, it is likely that the sEH inhibitors may be potential therapeutic drugs for neuropsychiatric diseases such as schizophrenia. (C) 2013 Elsevier Inc. All rights reserved.
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