期刊
BIOCHEMICAL PHARMACOLOGY
卷 166, 期 -, 页码 313-321出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2019.06.008
关键词
Caffeine; Long-term potentiation; Neuromodulation; Hippocampus; Adenosine receptors
资金
- Fundacion LaCaixa
- FEDER (QREN), through Programa Mais Centro [CENTRO-01-0246-FEDER-000010, CENTRO-07-ST24-FEDER-002006]
- Programa Operational Factores de Competitividade - COMPETE
- National funds via FCT - Fundacao para a Ciencia e a Tecnologia [POCI-01-0145-FEDER-031274, SFRH/BPD/85404/2012]
Caffeine is the most consumed psychoactive drug worldwide and its intake in moderate amounts prevents neurodegenerative disorders. However, the molecular targets of caffeine to modulate activity in brain circuits are ill-defined. By electrophysiologically recording synaptic transmission and plasticity in Schaffer fibers-CA1 pyramid synapses of mouse hippocampal slices, we characterized the impact of caffeine using a concentration reached in the brain parenchyma upon moderate caffeine consumption. Caffeine (50 mu M) facilitated synaptic transmission by 40%, while decreasing paired-pulse facilitation, and also decreased by 35% the amplitude of long-term potentiation (LTP). Clearance of extracellular adenosine with adenosine deaminase (2 U/mL) blunted all the effects of caffeine on synaptic transmission and plasticity. The A(1)R antagonist DPCPX (100 nM) only eliminated caffeine-induced facilitation of synaptic transmission while not affecting caffeine-induced depression of LTP; conversely, the genetic (using A(2A)R knockout mice) or the pharmacological blockade (with SCH58261, 50 nM) of A(2A)R eliminated the effect of caffeine on LTP while not affecting caffeine-induced facilitation of synaptic transmission. Finally, blockade of GABA(A) or of ryanodine receptors with bicuculline (10 mu M) or dantrolene (10 mu M), respectively, did not affect the ability of caffeine to alter synaptic transmission or plasticity. These results show that the effects of caffeine on synaptic transmission and plasticity in the hippocampus are selectively mediated by antagonizing adenosine receptors, where A(1)R are responsible for the impact of caffeine on synaptic transmission and A(2A)R regulate the impact of caffeine on LTP.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据