Monti Jaime M, Leopoldo Marcello, Jantos Héctor
Department of Pharmacology and Therapeutics, Clinics Hospital, 2833/602 Zudañez Street, Montevideo 11300, Uruguay.
Behav Brain Res. 2008 Aug 22;191(2):184-9. doi: 10.1016/j.bbr.2008.03.025. Epub 2008 Mar 25.
The effects of LP-44, a selective 5-HT7 receptor agonist, and of SB-269970, a selective 5-HT7 receptor antagonist, on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. The 5-HT7 receptor ligands were microinjected directly into the dorsal raphe nucleus (DRN) during the light period of the 12-h light/12-h dark cycle. Infusion of LP-44 (1.25-5.0 mM) into the DRN induced a significant reduction of rapid-eye-movement sleep (REMS) and of the number of REM periods. Similar effects were observed after the direct administration into the DRN of SB-269970 (0.5-1.0 mM). Pretreatment with a dose of SB-269970 (0.5 mM) that significantly affects sleep variables antagonized the LP-44 (2.5 mM)-induced suppression of REMS and of the number of REM periods. It is proposed that the suppression of REMS after microinjection of LP-44 into the DRN is related, at least in part, to the activation of GABAergic neurons in the DRN that contribute to long projections that reach, among others, the laterodorsal and pedunculopontine tegmental nuclei involved in the promotion of REMS.
在植入用于慢性睡眠记录的成年大鼠中，研究了选择性5-羟色胺7（5-HT7）受体激动剂LP-44和选择性5-HT7受体拮抗剂SB-269970对自发睡眠的影响。在12小时光照/12小时黑暗周期的光照期，将5-HT7受体配体直接微量注射到中缝背核（DRN）中。向DRN中注入LP-44（1.25 - 5.0 mM）可导致快速眼动睡眠（REMS）和REM期数量显著减少。将SB-269970（0.5 - 1.0 mM）直接注入DRN后也观察到类似效果。用显著影响睡眠变量的剂量SB-269970（0.5 mM）进行预处理，可拮抗LP-44（2.5 mM）诱导的REMS抑制和REM期数量减少。有人提出，向DRN中微量注射LP-44后对REMS的抑制至少部分与DRN中γ-氨基丁酸能神经元的激活有关，这些神经元形成的长投射可到达包括参与促进REMS的外侧背核和脚桥被盖核等多个脑区。
