Department of Psychology and Neuroscience, Baylor University, Waco, Texas, USA.
Institute of Biomedical Studies, Baylor University, Waco, Texas, USA.
Dev Psychobiol. 2024 Nov;66(7):e22543. doi: 10.1002/dev.22543.
Early life seizures are associated with a variety of behavioral comorbidities. Among the most prevalent of these are deficits in communication. Auditory communicative behaviors in mice, known as ultrasonic vocalizations (USVs), can be used to assess potential treatments. Agomelatine is a melatonin agonist that effectively reduces behavioral comorbidities of seizures in adults; however, its ability to attenuate seizure-induced communicative deficits in neonates is unknown. To address this, we administered C57 mice either saline or kainic acid (KA) on postnatal day (PD) 10. The mice then received either agomelatine or saline 1-h post-status epilepticus. On PD 11, we assessed the quantity of USVs produced, the duration, peak frequency, fundamental frequency, and amplitude of the vocalizations, as well as the call type utilization. We found that KA increased vocal production and reduced USV variability relative to controls. KA also increased USV duration and amplitude and significantly altered the types of calls produced. Agomelatine did not attenuate any of the deficits. Our study is the first to assess agomelatine's efficacy to correct USVs and thus provides an important point of context to the literature, indicating that despite its high therapeutic efficacy to attenuate other behavioral comorbidities of seizures, agomelatine's ability to correct neonatal communicative deficits is limited.
早期生活中的癫痫发作与多种行为共病有关。其中最常见的是沟通缺陷。在老鼠中，被称为超声波发声（USVs）的听觉交流行为可用于评估潜在的治疗方法。阿戈美拉汀是一种褪黑素激动剂，可有效减轻成人癫痫发作的行为共病；然而，其减轻新生儿癫痫发作引起的交流缺陷的能力尚不清楚。为了解决这个问题，我们在出生后第 10 天（PD）给 C57 小鼠注射盐水或海人酸（KA）。然后，在癫痫持续状态后 1 小时，小鼠接受阿戈美拉汀或盐水治疗。在 PD 11，我们评估了产生的 USVs 的数量、持续时间、峰值频率、基频和幅度，以及叫声类型的利用。我们发现 KA 增加了发声的产生并降低了 USV 的可变性相对于对照。KA 还增加了 USV 的持续时间和幅度，并显著改变了产生的叫声类型。阿戈美拉汀并没有减轻任何缺陷。我们的研究首次评估了阿戈美拉汀纠正 USVs 的功效，因此为文献提供了一个重要的背景点，表明尽管其具有很高的治疗效果来减轻癫痫发作的其他行为共病，但阿戈美拉汀纠正新生儿交流缺陷的能力是有限的。
