Selective Serotonin Reuptake Inhibitors and 5-HT2 Receptor Agonists Have Distinct, Sleep-state Dependent Effects on Postictal Breathing in Amygdala Kindled Mice.
Selective Serotonin Reuptake Inhibitors and 5-HT2 Receptor Agonists Have Distinct, Sleep-state Dependent Effects on Postictal Breathing in Amygdala Kindled Mice.
复制标题
选择性血清素再摄取抑制剂和 5-HT2 受体激动剂对杏仁核点燃小鼠的发作后呼吸具有明显的睡眠状态依赖性影响。
DOI：
10.1016/j.neuroscience.2023.01.016
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发表时间：
2023
期刊：
影响因子：
3.3
通讯作者：
Buchanan,GordonF
中科院分区：
文献类型：
--
作者：
Joyal,KatelynG;Petrucci,AlexandraN;Littlepage-Saunders,MydirahV;Boodhoo,NicoleA;Wendt,LinderH;Buchanan,GordonF
癫痫发作会导致严重的呼吸中断。睡眠引起的癫痫发作比清醒引起的癫痫发作引起更大的呼吸障碍，并且更经常导致癫痫中的突然意外死亡（SUDEP）。神经递质5-羟色胺（5-HT）在呼吸和睡眠-觉醒调节中起着重要作用。5-HT调节癫痫发作的敏感性和严重性，并且由癫痫发作失调。因此，癫痫发作对呼吸失调的影响可能是由于受损的5-HT神经传递。我们研究了癫痫发作前增加5-HT神经传递是否能改善发作后呼吸，以及癫痫发作诱导期间的睡眠状态如何有助于这些作用。我们用全身体积描记法对84只杏仁核点燃的小鼠进行了呼吸评估，这些小鼠预先接受了选择性5-羟色胺再摄取抑制剂（SSRI）或5-HT 2受体激动剂的治疗。SSRIs和5-HT 2受体激动剂在清醒状态下诱发癫痫发作后不同时间点增加发作后呼吸频率（fR）、潮气量（VT）和每分钟通气量（VE）。在NREM睡眠期间诱发癫痫发作后未观察到这些效应。SSRIs抑制发作和发作后呼吸暂停，与睡眠状态无关。SSRI西酞普兰和5-HT 2受体激动剂TCB-2和MK-212降低了清醒发作后不同时间点的呼吸变异性。只有MK-212降低呼吸变异性时，诱发癫痫发作在NREM睡眠。5-HT 2A拮抗剂MDL-11939降低了西酞普兰对fR、VT和VE的作用，并增强了其对癫痫发作后初期呼吸变异性的作用。这些结果表明，依赖或独立于5-HT 2受体家族的5-HT机制在正常呼吸恢复期间影响不同时间尺度的呼吸，并且某些肾上腺素能治疗在促进睡眠中出现的癫痫发作后呼吸方面可能不太有效。
Seizures can cause profound breathing disruptions. Seizures arising from sleep cause greater breathing impairment than those emerging from wakefulness and more often result in sudden unexpected death in epilepsy (SUDEP). The neurotransmitter serotonin (5-HT) plays a major role in respiration and sleep-wake regulation. 5-HT modulates seizure susceptibility and severity and is dysregulated by seizures. Thus, the impact of seizures on breathing dysregulation may be due to impaired 5-HT neurotransmission. We examined whether pharmacologically increasing 5-HT neurotransmission prior to seizures improves postictal breathing and how sleep-state during seizure induction contributes to these effects. We assessed breathing with whole-body plethysmography in 84 amygdala-kindled mice pre-treated with selective serotonin reuptake inhibitors (SSRI) or 5-HT2receptor agonists. SSRIs and 5-HT2agonists increased postictal breathing frequency (fR), tidal volume (VT), and minute ventilation (VE) at different timepoints following seizures induced during wakefulness. These effects were not observed following seizures induced during NREM sleep. SSRIs suppressed ictal and postictal apnea regardless of sleep state. The SSRI citalopram and the 5-HT2agonists TCB-2 and MK-212 decreased breathing variability following wake-occurring seizures at different postictal timepoints. Only MK-212 decreased breathing variability when seizures were induced during NREM sleep. The 5-HT2Aantagonist MDL-11939 reduced the effect of citalopram on fR, VT, and VE, and enhanced its effect on breathing variability in the initial period following a seizure. These results suggest that 5-HT mechanisms that are dependent on or independent from the 5-HT2family of receptors impact breathing on different timescales during the recovery of eupnea, and that certain serotonergic treatments may be less effective at facilitating postictal breathing following seizures emerging from sleep.