کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4179499 1276552 2008 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Phencyclidine-Induced Cognitive Deficits in Mice Are Improved by Subsequent Subchronic Administration of the Novel Selective α7 Nicotinic Receptor Agonist SSR180711
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی روانپزشکی بیولوژیکی
پیش نمایش صفحه اول مقاله
Phencyclidine-Induced Cognitive Deficits in Mice Are Improved by Subsequent Subchronic Administration of the Novel Selective α7 Nicotinic Receptor Agonist SSR180711
چکیده انگلیسی

BackgroundAccumulating evidence suggests that α7 nicotinic receptor (α7 nAChR) agonists could be potential therapeutic drugs for cognitive deficits in schizophrenia. The present study was undertaken to examine the effects of the novel selective α7 nAChR agonist SSR180711 on cognitive deficits in mice after repeated administration of the N-methyl-D-aspartate receptor antagonist phencyclidine (PCP).MethodsSaline or PCP (10 mg/kg/day for 10 days) was administered to mice. Subsequently, vehicle, SSR180711 (.3 or 3.0 mg/kg/day), SSR180711 (3.0 mg/kg/day) + the selective α7 nAChR antagonist methyllycaconitine (MLA; 3.0 mg/kg/day), or MLA (3.0 mg/kg/day) was administered IP for 2 consecutive weeks. Twenty-four hours after the final administration, a novel object recognition test was performed.ResultsThe PCP-induced cognitive deficits were significantly improved by subsequent subchronic (2-week) administration of SSR180711 (3.0 mg/kg). The effects of SSR180711 (3.0 mg/kg) were significantly antagonized by co-administration of MLA (3.0 mg/kg). Furthermore, Western blot analysis and immunohistochemistry revealed that levels of α7 nAChRs in the frontal cortex and hippocampus of the PCP (10 mg/kg/day for 10 days)-treated mice were significantly lower than those of saline-treated mice.ConclusionsThese findings suggest that repeated PCP administration significantly decreased the density of α7 nAChRs in the brain and that the α7 nAChR agonist SSR180711 could ameliorate cognitive deficits in mice after repeated administration of PCP. Therefore, α7 nAChR agonists including SSR180711 are potential therapeutic drugs for treating cognitive deficits in schizophrenic patients.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biological Psychiatry - Volume 63, Issue 1, 1 January 2008, Pages 92–97
نویسندگان
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