Department of Pharmacology and Therapeutics, School of Medicine Clinics Hospital. Montevideo 11600, Uruguay.
Behav Brain Res. 2013 Jul 15;249:65-74. doi: 10.1016/j.bbr.2013.04.024. Epub 2013 Apr 24.
The effects of WAY-208466, a selective 5-HT6 receptor agonist on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. Systemic administration of WAY-208466 during the light phase of the light-dark cycle significantly increased wakefulness (W) and reduced slow wave sleep (SWS), REM sleep (REMS) and the number of REMS periods. Pretreatment with the selective 5-HT6 receptor antagonist RO-399885 prevented the effects of the 5-HT6 receptor agonist on W, SWS and REMS. Direct infusion of WAY-208466 into the dorsal raphe nucleus, locus coeruleus, basal forebrain (horizontal limb of the diagonal band of Broca) or laterodorsal tegmental nucleus specifically decreased REMS without significantly altering W or SWS. In all instances the REMS suppression was dependent upon the reduction of REMS periods. The finding that WAY-208466 increases extracellular γ-aminobutyric acid (GABA) levels in the rat frontal cortex tends to suggest that the neurotransmitter could be involved in the 5-HT6 receptor agonist-induced disruption of the sleep-wake cycle. However, further studies are needed to resolve this issue.
研究了选择性 5-HT6 受体激动剂 WAY-208466 对植入慢性睡眠记录电极的成年大鼠自发睡眠的影响。在光-暗周期的光期给予全身 WAY-208466 显著增加觉醒（W）并减少慢波睡眠（SWS）、快速眼动睡眠（REMS）和 REMS 期数。选择性 5-HT6 受体拮抗剂 RO-399885 预处理可防止 5-HT6 受体激动剂对 W、SWS 和 REMS 的作用。WAY-208466 直接输注到中缝背核、蓝斑核、基底前脑（Broca 水平带的横向肢）或外侧背侧被盖核特异性减少 REMS，而对 W 或 SWS 无明显影响。在所有情况下，REMS 抑制都依赖于 REMS 期数的减少。WAY-208466 增加大鼠额叶皮质细胞外 γ-氨基丁酸（GABA）水平的发现表明，神经递质可能参与了 5-HT6 受体激动剂引起的睡眠-觉醒周期紊乱。然而，需要进一步的研究来解决这个问题。
