Amygdala Priming Mechanism Underlying the Panic Response

恐慌反应背后的杏仁核启动机制

• 批准号: 6341323
• 负责人: SHELLEY K THIELEN
• 金额: $ 2.7万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-23 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6341323
• 关键词: amygdala; antidepressants; avoidance behavior; behavior test; behavioral /social science research tag; bicuculline; blood pressure; conditioning; disease /disorder model; fenfluramine; heart rate; laboratory rat; panic disorder; psychopharmacology; psychophysiology; pulmonary respiration; serotonin inhibitor; yohimbine

Anxiety disorders are the most common of all mental health illnesses. Panic disorder (PD), a DSM recognized anxiety disorder, has a lifetime prevalence of 3.5%. The delay of treatment of this illness is further complicated by comorbidity with alcohol abuse or depression. These patients are also at increased risk of suicide. Rats bilaterally implanted with guide cannulae into the basolateral nucleus of the amygdala and injected for a maximum of 6 days with a subthreshold dose of the GABAA antagonist bicuculline methiodide exhibit an increase in heart rate (> 50 beats per minute), blood pressure, respiratory rate, and anxiety- like behavior, measured using the social interaction test on day 4 to 6 of drug treatment. The response exhibited by these rats is reminiscent of the symptoms experienced by panic disorder patients. Further, the BLA nucleus has been identified to be involved in the defense reaction as well as in conditioned fear- both responses are relevant to the development of the panic response. The objective of this research is utilize the primed rat to study the mechanisms underlying the panic response. Specifically, this research is aimed to: 1) determine the whether the panic-provoking agents yohimbine and fenfluramine are able to provoke similar responses in the BLA- primed rat; 2) determine if drugs effective in treating human panic attacks attenuate the panic response in the primed rat; and, 3) determine if the primed rat exhibits conditioned place avoidance. The methods used to explore the first aim will involve quantitating any change in heart rate, blood pressure, or respiratory rate during and after intravenous infusion of the panic provoking agent. Infusion of the drugs will be randomized and behavior will be measured after the monitoring period using the social interaction test. In this test the experimental rat will be paired with an untreated weight-matched (within 10 grams) rat in a 91 square cm arena for five minutes. Each rat will have been habituated to the arena and the lighting conditions prior to testing. Test duration will be 5 minutes. For the second aim, a Pavlovian conditioning test called conditioned place avoidance will be used to determine whether repeated intra- amygdala injections of BMI are aversive and therefore possibly indicative of the development of avoidance of the floor associated with the stimulus. Animals will be conditioned using tactile cues- floors constructed from perforated stainless steel or from stainless steel rods. For the third aim, BLA-primed rats will be treated twice daily for seven days with a prototypical SSRI or TCA and then challenged with an intra- amygdala injection of BMW. Treatments will be administered intraperitoneally, both acutely and chronically. The animal will be assessed for changes in response to the intra- amygdala injection of BMI. These three points will be used to study the underlying mechanism of the panic response. This mechanism of provoking the panic response is potentially beneficial in further understanding the neurobiology of the panic response on both the behavioral and cellular level.

焦虑症是所有心理健康疾病中最常见的。恐慌症(PD)是一种DSM认可的焦虑症，终生患病率为3.5%。这种疾病的延迟治疗由于与酗酒或抑郁的共病而进一步复杂化。这些患者的自杀风险也增加了。在大鼠双侧杏仁核底外侧核植入引导管，并注射阈值以下剂量的GABAA拮抗剂甲基荷包牡丹碱最多6天，大鼠表现出心率(&gt；每分钟50次)、血压、呼吸频率和焦虑样行为的增加，使用药物治疗第4至6天的社会互动测试。这些老鼠表现出的反应让人想起惊恐障碍患者所经历的症状。此外，BLA核已被发现参与防御反应和条件性恐惧--这两种反应都与恐慌反应的发展有关。这项研究的目的是利用被启动的大鼠来研究惊恐反应的潜在机制。具体地说，这项研究的目的是：1)确定引起恐慌的药物育亨宾和芬氟拉明是否能够在BLA引发的大鼠中引发类似的反应；2)确定有效治疗人类恐慌发作的药物是否减弱了引发BLA的大鼠的恐慌反应；以及3)确定引起恐慌的大鼠是否表现出条件性的位置回避。用于探索第一个目标的方法将涉及量化在静脉注射引发恐慌的药物期间和之后心率、血压或呼吸频率的任何变化。药物的输注将是随机的，并将在监测期后使用社会互动测试来测量行为。在这项测试中，实验大鼠将与一只未经处理的体重匹配(10克以内)的大鼠在91平方厘米的竞技场中配对5分钟。在测试之前，每只老鼠都已经习惯了竞技场和照明条件。测试持续时间为5分钟。对于第二个目的，将使用一种名为条件性位置回避的巴甫洛夫条件反射测试来确定反复在杏仁核内注射BMI是否是厌恶的，因此可能表明与刺激相关的下限回避的发展。动物将使用触觉提示-由穿孔不锈钢或不锈钢棒建造的地板-进行调节。对于第三个目的，BLA免疫的大鼠将接受为期七天的每天两次的典型SSRI或TCA治疗，然后在杏仁体内注射宝马。治疗将通过腹膜腔进行，既有急性的，也有慢性的。这只动物将被评估杏仁体内注射BMI后的变化。这三点将被用来研究恐慌反应的潜在机制。这种激发恐慌反应的机制可能有助于从行为和细胞水平上进一步了解恐慌反应的神经生物学。