Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, ES, Brazil.
Psychoneuroendocrinology. 2010 Jun;35(5):706-16. doi: 10.1016/j.psyneuen.2009.10.011. Epub 2009 Nov 22.
Conflicting clinical data on the relationship of panic disorder and thyroid diseases illustrate the need for a simpler approach using animal models. Defensive behaviors evoked by electrical or chemical stimulation of dorsal periaqueductal gray matter (DPAG) have been proposed as a model of panic attack. Therefore, the present study examined the effects of the anti-thyroid agent methimazole (MTZ) either on the panic-like behaviors induced by electrical stimulation of DPAG or the anxiety-like behaviors of rats exposed to the elevated plus-maze (EPM). Male Wistar rats bearing electrodes in the DPAG were stimulated with stepwise increased currents. Rats which displayed galloping at intensities below 60muA were retested following 5- and 10-day treatments with MTZ (0.6mg/kg/day, i.p.) or 10- and 15-day washout periods. MTZ effects on EPM performance were assessed in separate groups. MTZ-treated groups were compared to saline-treated controls. In other experiments, rats were similarly treated with MTZ and the blood was collected for hormone assays. The 10-day treatment with MTZ produced marked increases in the thresholds of exophthalmus (65%), immobility (75%), trotting (63%), galloping (56%), jumping (47%), defecation (114%) and micturition (85%). Effects outlasted the drug discontinuation. In contrast, MTZ had variable effects in the EPM, significantly increasing the open-arm exploration in 5-day treated and 10-day washout groups. Biochemical data revealed a small but significant decrease (13%) in free thyroxine in MTZ-treated groups. Although not significant, thyrotrophin levels showed a 111% increase following the 10-day treatment with MTZ. Selective attenuation by MTZ of DPAG-evoked defensive behaviors supports attenuation of panic attacks in hypothyroidism.
有关恐慌障碍和甲状腺疾病之间关系的临床数据相互矛盾，这说明需要采用更简单的方法，使用动物模型。通过电或化学刺激背侧periaqueductal 灰质（DPAG）引发的防御行为已被提议作为恐慌发作的模型。因此，本研究检查了抗甲状腺药物甲巯咪唑（MTZ）对 DPAG 电刺激诱导的类似恐慌行为或暴露于高架十字迷宫（EPM）的大鼠的焦虑样行为的影响。在 DPAG 中带有电极的雄性 Wistar 大鼠接受逐步增加的电流刺激。在强度低于 60μA 的情况下显示奔跑的大鼠，在接受 MTZ（0.6mg/kg/天，ip）治疗 5 天和 10 天或 10 天和 15 天洗脱期后进行重新测试。在单独的组中评估 MTZ 对 EPM 性能的影响。将 MTZ 处理组与盐水处理的对照组进行比较。在其他实验中，大鼠也用 MTZ 进行类似处理，并收集血液进行激素测定。10 天的 MTZ 治疗导致眼球突出（65％）、不动（75％）、小跑（63％）、奔跑（56％）、跳跃（47％）、排便（114％）和排尿（85％）的阈值显着增加。停药后效果仍持续。相比之下，MTZ 在 EPM 中有不同的作用，在 5 天治疗和 10 天洗脱组中显着增加了开放臂的探索。生化数据显示 MTZ 处理组的游离甲状腺素水平略有但显着降低（13％）。尽管不显着，但 MTZ 治疗 10 天后促甲状腺激素水平增加了 111％。MTZ 对 DPAG 诱发的防御行为的选择性衰减支持甲状腺功能减退症中恐慌发作的衰减。
