Sleep Research Laboratory, Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA 23507, USA.
Brain Res. 2012 May 3;1452:85-95. doi: 10.1016/j.brainres.2012.03.003. Epub 2012 Mar 8.
Systemic administration of the Group II metabotropic glutamate (mGlu) receptor agonist, LY379268 (LY37), dose-dependently suppresses rapid eye movement sleep (REM) whereas systemic administration of the mGlu II receptor antagonist, LY341495 (LY34), increases arousal. Group II mGlu receptors are highly expressed in the amygdala, a brain region involved in the regulation of sleep and arousal. To determine whether the amygdala is involved in mediating the effects of Group II mGlu agents on sleep, we microinjected LY37 and LY34 into the basal amygdala (BA) and the central nucleus of the amygdala (CNA) and recorded sleep and wakefulness. Wistar rats were implanted with electrodes for recording sleep and with bilateral cannulae aimed into BA for drug administration. Different groups of rats received bilateral microinjections of LY37 into BA at two dosage ranges (3.2 mM, 5.3 mM or 10.7 mM or 0.1 nM, 2.0 nM or 10.0 nM) or one dosage range of LY34 (1.0 nM, 30.0 nM or 60.0 nM). Microinjections into CNA were conducted at one dosage range for LY37 (0.1 nM, 2.0 nM or 10.0 nM) and for LY34 (1.0 nM, 30.0 nM or 60.0 nM). All drugs or vehicle alone were administered in a counterbalanced order at 5-day intervals. Following microinjection, sleep was recorded for 20 h. Microinjection of LY37 into BA at both nM and mM concentrations significantly decreased REM without significantly altering NREM, total sleep or wakefulness. The high dosage of LY34 in BA significantly suppressed NREM and total sleep. Microinjections of LY37 or LY34 into CNA had no significant impact on sleep. We suggest that Group II mGlu receptors may influence specific cells in BA that control descending output (via the CNA or bed nucleus of the stria terminalis) that in turn regulates pontine REM generator regions.
系统给予 II 组代谢型谷氨酸（mGlu）受体激动剂 LY379268（LY37），剂量依赖性地抑制快速眼动睡眠（REM），而系统给予 mGlu II 受体拮抗剂 LY341495（LY34），则增加觉醒。II 组 mGlu 受体在杏仁核中高度表达，杏仁核是参与调节睡眠和觉醒的脑区。为了确定杏仁核是否参与调节 II 组 mGlu 药物对睡眠的影响，我们将 LY37 和 LY34 微注射到基底杏仁核（BA）和杏仁核中央核（CNA）中，并记录睡眠和觉醒。Wistar 大鼠植入用于记录睡眠的电极，并植入双侧导管，用于 BA 中的药物给药。不同组的大鼠接受双侧 BA 中的 LY37 微注射，剂量范围为 3.2mM、5.3mM 或 10.7mM 或 0.1nM、2.0nM 或 10.0nM，或 LY34 的一个剂量范围（1.0nM、30.0nM 或 60.0nM）。LY37 的 CNA 中的微注射剂量范围为 0.1nM、2.0nM 或 10.0nM，LY34 的微注射剂量范围为 1.0nM、30.0nM 或 60.0nM。所有药物或单独的载体均以 5 天间隔的平衡方式给药。微注射后，记录 20 小时的睡眠。BA 中的 LY37 的 nM 和 mM 浓度的微注射均显著降低 REM，而不显著改变 NREM、总睡眠或觉醒。BA 中的高剂量 LY34 显著抑制 NREM 和总睡眠。LY37 或 LY34 微注射到 CNA 对睡眠没有显著影响。我们认为，II 组 mGlu 受体可能影响控制下行输出的 BA 中的特定细胞（通过 CNA 或终纹床核），进而调节脑桥 REM 发生器区域。
