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The H‐2 Receptor Antagonist Cimetidine Blocks Kainic Acid Toxicity in Hippocampus as Effectively as the NMDA Receptor Antagonist MK‐801
Author(s) -
Rojiani Amyn M,
Ambegaoankar Megha,
Gordon Marcia N,
Breitner John C.S.,
Morgan Dave
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a20-b
Subject(s) - cimetidine , kainic acid , antagonist , nmda receptor , dizocilpine , neurotoxicity , receptor antagonist , pharmacology , hippocampus , neuroprotection , chemistry , medicine , endocrinology , receptor , toxicity , glutamate receptor
Individuals using H‐2 receptor antagonists have been reported to have a reduced prevalence of dementia. Our prior work has demonstrated that the H‐2 antagonist cimetidine did not significantly affect amyloid deposition in APP transgenic mice. The current study was carried out to determine if neuroprotection is an alternative mechanism by which cimetidine may reduce the risk of dementia. 6 mo. old mice were assigned randomly to one of three groups. Group 1 was injected intraventricularly with kainic acid (KA, 150 μg/1μl; n = 6). Group 2 was pretreated with cimetidine 60 minutes prior to the KA injection (50 mg/kg, IP; n = 9). Group 3 was treated with MK‐801 one minute prior to KA injection (1μg/1μl intraventricular; n =7). 7 days after the KA injections brains were removed, fixed, cryoprotected, sectioned and stained with cresyl violet for Nissl. The regions of cellular necrosis in the hippocampus were measured by image analysis. Data were statistically analyzed. Cimetidine protected mice from neurotoxicity caused by intrahippocampal Kainic acid injections to the same extent as mice injected with the prototypical NMDA receptor antagonist MK‐801. These data suggest that cimetidine use may have a protective effect in dementia by diminishing potential excitotoxic mechanisms that may contribute to the pathogenesis of Alzheimer's disease.