Caffeine Reverts Memory But Not Mood Impairment in a Depression-Prone Mouse Strain with Up-Regulated Adenosine A_2A Receptor in Hippocampal Glutamate Synapses

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• 作者：Nuno J. Machado ; Ana Patrícia Simões ; Henrique B. Silva…
• 关键词：Caffeine ; Adenosine A2A receptors ; Memory ; Depression ; Synaptic plasticity ; Glutamate release
• 刊名：Molecular Neurobiology
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：54
• 期：2
• 页码：1552-1563
• 全文大小：
• 刊物主题：Neurosciences; Neurobiology; Cell Biology; Neurology;
• 出版者：Springer US
• ISSN：1559-1182
• 卷排序：54

文摘

Caffeine prophylactically prevents mood and memory impairments through adenosine A_2A receptor (A_2AR) antagonism. A_2AR antagonists also therapeutically revert mood and memory impairments, but it is not known if caffeine is also therapeutically or only prophylactically effective. Since depression is accompanied by mood and memory alterations, we now explored if chronic (4 weeks) caffeine consumption (0.3 g/L) reverts mood and memory impairment in helpless mice (HM, 12 weeks old), a bred-based model of depression. HM displayed higher immobility in the tail suspension and forced swimming tests, greater anxiety in the elevated plus maze, and poorer memory performance (modified Y-maze and object recognition). HM also had reduced density of synaptic (synaptophysin, SNAP-25), namely, glutamatergic (vGluT1; −22 ± 7 %) and GABAergic (vGAT; −23 ± 8 %) markers in the hippocampus. HM displayed higher A_2AR density (72 ± 6 %) in hippocampal synapses, an enhanced facilitation of hippocampal glutamate release by the A_2AR agonist, CGS21680 (30 nM), and a larger LTP amplitude (54 ± 8 % vs. 21 ± 5 % in controls) that was restored to control levels (30 ± 10 %) by the A_2AR antagonist, SCH58261 (50 nM). Notably, caffeine intake reverted memory deficits and reverted the loss of hippocampal synaptic markers but did not affect helpless or anxiety behavior. These results reinforce the validity of HM as an animal model of depression by showing that they also display reference memory deficits. Furthermore, caffeine intake selectively reverted memory but not mood deficits displayed by HM, which are associated with an increased density and functional impact of hippocampal A_2AR controlling synaptic glutamatergic function.