Chronic treatment with DCPCX, an adenosine A1 antagonist, worsens long-term memory

NEUROSCIENCE LETTERS

卷:548

Article

Vollert, Craig¹  Forkuo, Gloria S.¹  Bond, Richard A.¹  Eriksen, Jason L.¹ 

[1] Univ Houston, Dept Pharmacol & Pharmaceut Sci, Houston, TX 77204 USA

关键词: Alzheimer's disease;    Adenosine A(1) antagonist;    Chronic treatment;    Impaired learning;    Anxiolytic;   

DOI  :  10.1016/j.neulet.2013.05.052

来源: Elsevier

【 摘 要 】

Alzheimer's disease is characterized by progressive cognitive disturbances and neurotransmitter dysfunction. Previous studies targeting the adrenergic A(1) pathway suggest that this plays a role in cognitive impairment in Alzheimer's disease. Previous studies have reported that acute treatment with A(1) antagonists appears to improve behavioral deficits in rodent models of memory and behavioral impairment. In this study, we addressed whether the chronic administration of 8-cyclopentyl-1,3-dipropylxanthine, a potent and selective adenosine A(1) antagonist, could reverse the memory deficits found in aged APP-swe/PS1dE9 mice. Chronic treatment did not improve memory in the APPswe/PS1dE9 mouse model and resulted in reduced exploratory behavior, suggestive of reduced anxiety, and a worsening of long-term memory in nontransgenic mice. These results have important implications for understanding the mechanisms of A(1) receptor modulation as a target in Alzheimer's disease therapy. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

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