کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8998427 1115629 2005 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
GABAB receptor antagonist SGS742 improves spatial memory and reduces protein binding to the cAMP response element (CRE) in the hippocampus
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
GABAB receptor antagonist SGS742 improves spatial memory and reduces protein binding to the cAMP response element (CRE) in the hippocampus
چکیده انگلیسی
Memory storage in the brain requires protein synthesis initiated through signaling pathways that control transcription. Such mechanisms are under active investigation for therapies in disorders involving cognitive dysfunction. Long-term memory can be improved by inhibiting activation or reducing expression of transcription factors such as ATF4/CREB2 and some C/EBP family members which appear to serve as memory suppressors. Here, we provide evidence that GABAB receptor antagonists may enhance cognition, at least in part, by this mechanism. We tested a GABAB receptor antagonist, SGS742 (CGP36742), on hippocampal-dependent memory and hippocampal nuclear CRE-binding activity in rats. As a result, acute in vivo administration of SGS742 both improved memory and reduced total hippocampal CRE-binding activity of which a large proportion in the basal state could be immunoneutralized with CREB2 antibodies. Consistent with its activity on information storage mechanisms, acute SGS742 effectively improved long-term memory in retrograde protocols, in which drug was given at times when memory formation can be interrupted by blocking new protein production. In conclusion, GABAB antagonists may provide a pharmacological therapy for cognitive impairment, sharing mechanistic features with genetic approaches to reduce CREB2 activity and to augment long-term memory.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 48, Issue 7, June 2005, Pages 956-964
نویسندگان
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