Caffeine and adenosine A2a receptor antagonists prevent β-amyloid (25–35)-induced cognitive deficits in mice
2007
Consumption of caffeine, an adenosine receptor antagonist, was found to be inversely associated with the incidence of Alzheimer's disease. Moreover, caffeine protects cultured neurons against β-amyloid-induced toxicity, an effect mimicked by adenosine A2A but not A1 receptor antagonists. We now tested if caffeine administration would prevent β-amyloid-induced cognitive impairment in mice and if this was mimicked by A2A receptor blockade. One week after icv administration of the 25–35 fragment of β-amyloid (Aβ, 3 nmol), mice displayed impaired performance in both inhibitory avoidance and spontaneous alternation tests. Prolonged treatment with caffeine (1 mg/ml) had no effect alone but prevented the Aβ-induced cognitive impairment in both tasks when associated with acute caffeine (30 mg/kg) 30 min treatment before Aβ administration. The same protective effect was observed after subchronic (4 days) treatment with daily injections of either caffeine (30 mg/kg) or the selective adenosine A2A receptor antagonist SCH58261 (0.5 mg/kg). This provides the first direct in vivo evidence that caffeine and A2A receptor antagonists afford a protection against Aβ-induced amnesia, which prompts their interest for managing Alzheimer's disease.
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