Department of Pharmacology and Therapeutics, School of Medicine, Clinics Hospital, 2833/602 Zudanez Street, Montevideo 11600, Uruguay.
Behav Brain Res. 2011 Jan 1;216(1):381-8. doi: 10.1016/j.bbr.2010.08.020. Epub 2010 Aug 21.
The effects of the 5-HT₆ receptor antagonists SB-399885 (2.5, 5 and 10 mg/kg) and RO-4368554 (2.5, 5 and 10 mg/kg) and of the 5-HT(2A) receptor antagonist EMD 281014 (2.5, 5 and 10 mg/kg) were studied in rats implanted for chronic sleep procedures. Administration of 10 mg/kg SB-399885, i.p., to rats 2 h after the beginning of the light phase of the light-dark cycle caused a significant increase of wakefulness (W) and a reduction of slow wave sleep (SWS), REM sleep (REMS) and the number of REM periods during 6-h recording sessions. Light sleep was increased after the whole range of doses. The increase of W and reduction of SWS and REMS occurred predominantly during the first 2-h period whereas light sleep was augmented over the first and the second 2-h recording periods. Injection of RO-4368554 (10 mg/kg, i.p.) 2 h after the beginning of the light period significantly increased W and reduced SWS and REMS during the first 2-h recording period. Administration of EMD 281014 (10 mg/kg, i.p.) during the light phase significantly increased SWS and reduced light sleep during 6-h sessions. REMS and the number of REM period were reduced with the entire range of doses. The reduction of REMS and light sleep and the increase of SWS occurred predominantly during the first and the second 2-h of recording, respectively. Injection of SB-399885 (10 mg/kg, i.p.) 2 h after the beginning of the dark period induced a significant reduction of REMS during the first 2-h of recording. In contrast, RO-4368554 did not modify values corresponding to sleep variables during the dark period. Treatment with EMD 281014 (2.5-10 mg/kg, i.p.) during the dark phase significantly increased SWS during the second 2-h period. Our study supports the proposal that blockade of postsynaptic 5-HT₆ receptors with systemic administration of SB-399885 and RO-4368554 increases W and reduces SWS and REMS during the light phase of the sleep-wake cycle. SB-399885 also induces a suppression of REMS during the dark period. It was confirmed, in addition, that administration of the 5-HT(2A) receptor antagonist EMD 281014 enhances SWS during both phases of the light-dark cycle in the rat.
5-HT₆受体拮抗剂 SB-399885（2.5、5 和 10 mg/kg）和 RO-4368554（2.5、5 和 10 mg/kg）以及 5-HT（2A）受体拮抗剂 EMD 281014（2.5、5 和 10 mg/kg）对慢性睡眠程序植入大鼠的影响进行了研究。在光-暗周期的光相开始后 2 小时，腹腔注射 10 mg/kg SB-399885 可显著增加觉醒（W）并减少慢波睡眠（SWS）、快速眼动睡眠（REMS）和 REM 期的数量在 6 小时记录期间。全剂量范围后轻睡眠增加。W 的增加和 SWS 和 REMS 的减少主要发生在最初的 2 小时期间，而轻睡眠则在前两个 2 小时记录期间增加。在光期开始后 2 小时腹腔注射 RO-4368554（10 mg/kg）可显著增加第一个 2 小时记录期间的 W 和减少 SWS 和 REMS。在光相期间给予 EMD 281014（10 mg/kg，腹腔内）可显著增加 SWS，并减少 6 小时期间的轻睡眠。用整个剂量范围给药可减少 REMS 和 REM 期的数量。REMS 和轻睡眠的减少以及 SWS 的增加主要发生在记录的前两个 2 小时内，分别。在暗期开始后 2 小时腹腔注射 SB-399885（10 mg/kg）可显著减少第一个 2 小时记录期间的 REMS。相比之下，RO-4368554 不会改变暗期对应于睡眠变量的值。在暗期期间用 EMD 281014（2.5-10 mg/kg，腹腔内）治疗可显著增加第二个 2 小时期间的 SWS。我们的研究支持这样的假设，即通过全身给予 SB-399885 和 RO-4368554 阻断突触后 5-HT₆ 受体可增加 W 并减少睡眠-觉醒周期光相期间的 SWS 和 REMS。SB-399885 还会在暗期抑制 REMS。此外，还证实了在大鼠的明暗周期的两个阶段，给予 5-HT（2A）受体拮抗剂 EMD 281014 可增强 SWS。
