Kimura-Takeuchi M, Inoué S
Institute for Medical and Dental Engineering, Tokyo Medical and Dental University, Japan.
Brain Res Bull. 1993;31(1-2):33-7. doi: 10.1016/0361-9230(93)90007-x.
In an attempt to investigate the effects on sleep modulation of order of administration of two substances, sequential intracerebroventricular (ICV) infusions of muramyl dipeptide (MDP, 1.0 nmol) and uridine (5.0 pmol) were conducted in freely behaving rats. To eliminate the influence of intermittent infusions on their behavior, the rats were continuously ICV infused with physiological saline solution, which did not affect their normal sleep-waking dynamics. Under these experimental conditions, uridine infusion (2400-0500 h) attenuated the enhancement of slow-wave sleep (SWS) caused by prior infusion of MDP (1900-2400 h) to the baseline level and, thus, did not exert a sleep-promoting property. In contrast, MDP infusion (2400-0500 h) further potentiated the SWS-enhancing activity of preinfused uridine (1900-2400 h). A single infusion of MDP or uridine (2400-0500 h) similarly enhanced SWS. These results demonstrate that observed differences in the induction and maintenance of sleep are dependent upon the order of exogenously infused uridine and MDP. The time sequence per se of these sleep substances may be responsible for the differential temporal changes in sleep. It is, therefore, assumed that a crucial order of multiple sleep substances may dynamically and differentially regulate sleep in the brain.
为了研究两种物质给药顺序对睡眠调节的影响，对自由活动的大鼠进行了依次脑室内（ICV）注射胞壁酰二肽（MDP，1.0纳摩尔）和尿苷（5.0皮摩尔）的实验。为消除间歇性注射对大鼠行为的影响，持续向大鼠脑室内注射生理盐水，这并未影响其正常的睡眠-觉醒动态。在这些实验条件下，尿苷注射（24:00 - 05:00）将先前注射MDP（19:00 - 24:00）所引起的慢波睡眠（SWS）增强减弱至基线水平，因此，尿苷并未发挥促睡眠特性。相反，MDP注射（24:00 - 05:00）进一步增强了预先注射尿苷（19:00 - 24:00）对SWS的增强作用。单次注射MDP或尿苷（24:00 - 05:00）同样增强了SWS。这些结果表明，观察到的睡眠诱导和维持方面的差异取决于外源性注射尿苷和MDP的顺序。这些睡眠物质本身的时间顺序可能是睡眠发生不同时间变化的原因。因此，可以推测多种睡眠物质的关键顺序可能在大脑中动态且差异性地调节睡眠。
