Department of Anatomy & Cell Biology, Indiana University School of Medicine, Indianapolis, IN, United States.
Prog Neuropsychopharmacol Biol Psychiatry. 2013 Jul 1;44:248-56. doi: 10.1016/j.pnpbp.2013.02.014. Epub 2013 Mar 21.
Rats treated with three daily urocortin 1 (UCN) injections into the basolateral amygdala (BLA; i.e., UCN/BLA-primed rats) develop prolonged anxiety-associated behavior and vulnerability to panic-like physiological responses (i.e., tachycardia, hypertension and tachypnea) following intravenous infusions of 0.5 M sodium lactate (NaLac, an ordinarily mild interoceptive stressor). In these UCN-primed rats, the osmosensitive subfornical organ (SFO) may be a potential site that detects increases in plasma NaLac and mobilizes panic pathways since inhibiting the SFO blocks panic following NaLac in this model. Furthermore, since SFO neurons synthesize angiotensin II (A-II), we hypothesized that the SFO projects to the BLA and releases A-II to mobilizing panic responses in UCN/BLA-primed rats following NaLac infusions. To test this hypothesis, rats received daily bilateral injections of UCN or vehicle into the BLA daily for 3 days. Five to seven days following the intra-BLA injections, we microinjected either the nonspecific A-II type 1 (AT1r) and 2 (AT2r) receptor antagonist saralasin, or the AT2r-selective antagonist PD123319 into the BLA prior to the NaLac challenge. The UCN/BLA-primed rats pre-injected with saralasin, but not PD123319 or vehicle, had reduced NaLac-induced anxiety-associated behavior and panic-associated tachycardia and tachypnea responses. We then confirmed the presence of AT1rs in the BLA using immunohistochemistry which, combined with the previous data, suggest that A-II's panicogenic effects in the BLA is AT1r dependent. Surprisingly, the SFO had almost no neurons that directly innervate the BLA, which suggests an indirect pathway for relaying the NaLac signal. Overall these results are the first to implicate A-II and AT1rs as putative neurotransmitter-receptors in NaLac induced panic-like responses in UCN/BLA-primed rats.
经三次每日单侧杏仁核基底外侧核（BLA）尿皮质素 1（UCN）注射处理的大鼠，在静脉输注 0.5 M 乳酸钠（NaLac，一种通常温和的内感受性应激源）后，会发展出持久的焦虑相关行为和易发生恐慌样生理反应（即心动过速、高血压和呼吸急促）。在这些 UCN 预处理的大鼠中，渗透压敏感的终板下器官（SFO）可能是一个潜在的位点，可以检测到血浆 NaLac 的增加，并动员恐慌途径，因为在该模型中，抑制 SFO 可阻止 NaLac 后的恐慌。此外，由于 SFO 神经元合成血管紧张素 II（A-II），我们假设 SFO 投射到 BLA，并在 UCN/BLA 预处理大鼠输注 NaLac 后释放 A-II 以动员恐慌反应。为了验证这一假设，大鼠每天接受双侧 UCN 或载体注射到 BLA 中，连续 3 天。在 BLA 内注射后 5 到 7 天，我们在 NaLac 挑战前，将非特异性 A-II 型 1（AT1r）和 2（AT2r）受体拮抗剂沙拉沙林，或 AT2r 选择性拮抗剂 PD123319 微注射到 BLA 中。用沙拉沙林预处理的 UCN/BLA 预处理大鼠，但不是 PD123319 或载体，其 NaLac 诱导的焦虑相关行为和恐慌相关心动过速和呼吸急促反应减少。然后，我们使用免疫组织化学证实了 BLA 中存在 AT1r，这与之前的数据相结合，表明 A-II 在 BLA 中的恐慌作用依赖于 AT1r。令人惊讶的是，SFO 几乎没有直接支配 BLA 的神经元，这表明存在一种传递 NaLac 信号的间接途径。总的来说，这些结果首次表明 A-II 和 AT1rs 作为 UCN/BLA 预处理大鼠中 NaLac 诱导的恐慌样反应的潜在神经递质受体。
