Serotonergic agents act on 5-HT(3) receptors in the brain to block seizure-induced respiratory arrest in the DBA/1 mouse model of SUDEP.
Serotonergic agents act on 5-HT(3) receptors in the brain to block seizure-induced respiratory arrest in the DBA/1 mouse model of SUDEP.
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DOI：
10.1016/j.yebeh.2016.09.034
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发表时间：
2016-11
期刊：
影响因子：
--
通讯作者：
Feng HJ
中科院分区：
文献类型：
--
作者：
Faingold CL;Randall M;Zeng C;Peng S;Long X;Feng HJ
增强5-羟色胺（5-羟色胺，5-HT）作用的药物，包括几种选择性5-羟色胺再摄取抑制剂（SSRI），可降低对癫痫猝死（SUDEP）DBA/1小鼠模型中导致死亡的癫痫诱导呼吸骤停（S-IRA）的敏感性。然而，目前尚不清楚特异性5-HT受体在这些药物的作用中是否重要，以及脑是否是这些药物在该SUDEP模型中的主要作用部位。本研究检测了影响5-HT 3受体亚型对S-IRA的作用，以及脑室内（ICV）微量注射SSRI是否会降低DBA/1小鼠S-IRA的易感性。数据表明，全身给予SR 57227（一种5-HT 3激动剂）在不阻断癫痫发作的剂量下可有效阻断S-IRA，同时给予5-HT 3拮抗剂昂丹司琼可消除SSRI（氟西汀）的S-IRA阻断作用。在本研究中，脑室内给予氟西汀也能够阻断S-IRA而不阻断癫痫发作。这些结果表明，5-HT_3受体在多巴胺能药物如SSRIs阻断S-IRA中起重要作用，这与先前观察到的DBA小鼠脑干中5-HT_3受体的异常表达一致。总之，这些数据表明，全身给药的多巴胺能药物的作用，至少在大脑中的一部分，以减少DBA/1小鼠的S-IRA的易感性，5-HT 3受体可能是重要的这种效果。
Drugs that enhance the action of serotonin (5-hydroxytrypamine, 5-HT), including several selective serotonin reuptake inhibitors (SSRIs), reduce susceptibility to seizureinduced respiratory arrest (S-IRA) that leads to death in the DBA/1 mouse model of sudden unexpected death in epilepsy (SUDEP). However, it is not clear if specific 5-HT receptors are important in the action of these drugs and whether the brain is the major site of action of these agents in this SUDEP model. The current study examined the actions of agents that affect the 5-HT3 receptor subtype on S-IRA and whether intracerebroventricular (ICV) microinjection of an SSRI would reduce S-IRA susceptibility in DBA/1 mice. The data indicate that systemic administration of SR 57227, a 5-HT3 agonist, was effective in blocking S-IRA in doses that did not block seizures, and the S-IRA blocking effect of the SSRI, fluoxetine, was abolished by co-administration of a 5-HT3 antagonist, ondansetron. Intracerebroventricular administration of fluoxetine in the present study was also able to block S-IRA without blocking seizures. These findings suggest that 5-HT3 receptors play an important role in the block of S-IRA by serotonergic agents, such as SSRIs, which is consistent with the abnormal expression of 5-HT3 receptors in the brainstem of DBA mice observed previously. Taken together, these data indicate that systemically administered serotonergic agents act, at least in part in the brain, to reduce S-IRA susceptibility in DBA/1 mice and that 5-HT3 receptors may be important to this effect.
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