Pietersen A N, Lancaster D M, Patel N, Hamilton J B, Vreugdenhil M
Department of Neurophysiology, Division of Neuroscience, School of Medicine, University of Birmingham, Vincent Drive, Birmingham, West Midlands B15 2TT, United kingdom.
Neuropharmacology. 2009 Feb;56(2):481-92. doi: 10.1016/j.neuropharm.2008.10.001. Epub 2008 Oct 17.
Adenosine serves as a homeostatic factor, regulating hippocampal activity through A(1) receptor-mediated inhibition. Gamma frequency oscillations, associated with cognitive functions, emerge from increased network activity. Here we test the hypothesis that hippocampal gamma oscillations are modulated by ambient adenosine levels. In mouse hippocampal slices exogenous adenosine suppressed the power of both kainate-induced gamma oscillations and spontaneous gamma oscillations, observed in a subset of slices in normal aCSF. Kainate-induced gamma oscillation power was suppressed by the A(1) receptor agonist PIA and potentiated by the A(1) receptor antagonist 8-CPT to three times matched control values with an EC(50) of 1.1microM. 8-CPT also potentiated spontaneous gamma oscillation power to five times control values. The A(2A) receptor agonist CGS21680 potentiated kainate-induced gamma power to two times control values (EC(50) 0.3nM), but this effect was halved in the presence of 8-CPT. The A(2A) receptor antagonist ZM241385 suppressed kainate-induced gamma power. The non-selective adenosine receptor antagonist caffeine induced gamma oscillations in slices in control aCSF and potentiated both kainate-induced gamma and spontaneous gamma oscillations to three times control values (EC(50) 28muM). Decreasing endogenous adenosine levels with adenosine deaminase increased gamma oscillations. Increasing endogenous adenosine levels with the adenosine kinase inhibitor 5-iodotubericidin suppressed gamma oscillations. Partial hypoxia-induced suppression of gamma oscillations could be prevented by 8-CPT. These observations indicate that gamma oscillation strength is powerfully modulated by ambient levels of adenosine through A(1) receptors, opposed by A(2A) receptors. Increased gamma oscillation strength is likely to contribute to the beneficial cognitive effects of caffeine.
腺苷作为一种稳态因子，通过A(1)受体介导的抑制作用调节海马体活动。与认知功能相关的γ频率振荡源于网络活动的增加。在此，我们检验海马体γ振荡受周围腺苷水平调节这一假说。在小鼠海马体切片中，外源性腺苷抑制了在正常人工脑脊液中一部分切片所观察到的红藻氨酸诱导的γ振荡和自发γ振荡的功率。红藻氨酸诱导的γ振荡功率被A(1)受体激动剂PIA抑制，并被A(1)受体拮抗剂8-CPT增强至对照值的三倍，其半数有效浓度（EC(50)）为1.1微摩尔。8-CPT还将自发γ振荡功率增强至对照值的五倍。A(2A)受体激动剂CGS21680将红藻氨酸诱导的γ功率增强至对照值的两倍（EC(50) 0.3纳摩尔），但在存在8-CPT的情况下，这种效应减半。A(2A)受体拮抗剂ZM241385抑制红藻氨酸诱导的γ功率。非选择性腺苷受体拮抗剂咖啡因在对照人工脑脊液中诱导切片产生γ振荡，并将红藻氨酸诱导的γ振荡和自发γ振荡均增强至对照值的三倍（EC(50) 28微摩尔）。用腺苷脱氨酶降低内源性腺苷水平会增加γ振荡。用腺苷激酶抑制剂5-碘杀结核菌素增加内源性腺苷水平会抑制γ振荡。8-CPT可预防部分缺氧诱导的γ振荡抑制。这些观察结果表明，γ振荡强度受到周围腺苷水平通过A(1)受体的强烈调节，A(2A)受体则起相反作用。γ振荡强度增加可能有助于咖啡因产生有益的认知效应。
