Действие агониста TAAR1 RO 5263397 на дискинезию, вызываемую инъекцией α-NETA

Авторы

DOI:

https://doi.org/10.33910/2687-1270-2023-4-3-346-355

Ключевые слова:

следовые амины, рецепторы следовых аминов, TAAR1, TAAR5, α-NETA, дискинезия, нокаутные мыши, агонист TAAR1 RO5263397

Аннотация

В настоящее время собрано достаточно данных о роли следовых аминов (СА) как нейромодуляторов в центральной нервной системе млекопитающих. СА имеют структурное сходство с классическими биогенными аминами, а изменения их концентрации связаны с различными психическими расстройствами. В центральной нервной системе человека широко экспрессируются два представителя семейства рецепторов СА — TAAR1 и TAAR5. В первой части исследования изучены поведенческие эффекты инъекции α-NETA (2-(alpha-naphthoyl) ethyltrimethylammonium iodide, 10 мг/кг, внутрибрюшинно) на мышей с нокаутом TAAR5 (KO TAAR5) и на мышей дикого типа (WT). Во второй части исследовано влияние агониста TAAR1, RO 5263397, на дискинезию, вызванную инъекцией α-NETA, у мышей-самцов C57BL/6. Было установлено, что инъекция α-NETA (10 мг/кг) вызывает дискинезию как у мышей дикого типа, так и у мышей KO TAAR5, что позволяет предположить отсутствие связи между дискинезией, индуцированной α-NETA, и рецепторами TAAR5. Во второй части исследования было установлено, что предварительное введение высокой дозы (1 мг/кг) агониста TAAR1 ингибирует дискинезию, индуцированную α-NETA, через 90 минут после инъекции. Кроме того, предварительное введение агониста TAAR1 существенно снижает возникновение длительных тонических спазмов. Таким образом полученные данные позволяют предположить, что агонисты TAAR1 перспективны для лечения определенных форм дискинезии.

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Опубликован

31.10.2023

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Экспериментальные статьи