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Strychnine and Taurine Modulation of Amygdala-associated Anxiety-like Behavior is ‘State’ Dependent

机译:杏仁核相关的焦虑样行为的马甲和牛磺酸调节是状态依赖的

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摘要

Strychnine-sensitive glycine receptors are expressed in many adult forebrain regions, yet the biological function of these receptors outside the spinal cord/brainstem is poorly understood. We have recently shown that rat lateral/basolateral amygdala neurons express strychnine-sensitive glycine-gated currents whose pharmacological and molecular characteristics are consistent with those established for classic ligand-gated chloride channels. The current studies were undertaken to establish the behavioral role, if any, of these strychnine-sensitive glycine receptors. Adult Long-Evans male rats were implanted with guide cannulae targeted at the lateral amygdala and were micro-injected with standard artificial cerebrospinal fluid with or without various doses of strychnine or taurine. Anxiety-like behaviors were assessed with the elevated plus-maze or the light/dark box. In the elevated plus maze, strychnine decreased closed-arm time and increased open-arm time, suggestive of an anxiolytic effect. Similarly, strychnine produced a modest anxiolytic effect in the light/dark box. Post-hoc analysis of ‘open-arm’ time and ‘light-side’ time indicated that aCSF-treated animals were distributed into two apparent groups that displayed either high or low amounts of anxiety-like behavior in a given apparatus. Surprisingly, the pharmacological effects of both strychnine and taurine in these assays were dependent upon a given animal’s behavioral phenotype. Together, these findings are significant because they suggest that the basal ‘emotional state’ of the animal could influence the behavioral outcome associated with drug application directly into the lateral/basolateral amygdala. Furthermore, our findings also suggest that compounds acting at amygdala strychnine-sensitive glycine receptors may actively modulate this basal anxiety-like state.
机译:在许多成年前脑区域中都表达了士的宁敏感的甘氨酸受体,但人们对这些受体在脊髓/脑干以外的生物学功能知之甚少。我们最近显示,大鼠外侧/基底外侧杏仁核神经元表达士的宁敏感的甘氨酸门控电流,其药理学和分子特性与经典配体门控氯化物通道建立的一致。进行了当前的研究来确定这些对士的宁敏感的甘氨酸受体的行为作用,如果有的话。将成年的Long-Evans雄性大鼠植入导向杏仁核外侧的引导套管,并用标准的人工脑脊液微量注射,并注入或不注入不同剂量的士的宁或牛磺酸。用升高的迷宫或明/暗框评估类似焦虑的行为。在高架迷宫中,士的宁减少了合臂时间并增加了合臂时间,提示抗焦虑作用。同样,士的宁在明/暗盒中产生适度的抗焦虑作用。对“张开双臂”时间和“光侧”时间的事后分析表明,经脑脊液治疗的动物被分为两个明显的组,在给定设备中显示出高或低水平的焦虑样行为。出乎意料的是,在这些试验中,士的宁和牛磺酸的药理作用均取决于给定动物的行为表型。总之,这些发现具有重要意义,因为它们表明动物的基础“情绪状态”可能会影响与药物直接应用于外侧/基底外侧杏仁核相关的行为结果。此外,我们的发现还表明,作用于杏仁核对鞘氨醇敏感的甘氨酸受体的化合物可能会主动调节这种基础性焦虑样状态。

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