Grupo de Neurociencias, Laboratorio de Canabinoides, Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico.
Pharmacol Biochem Behav. 2012 Dec;103(2):308-12. doi: 10.1016/j.pbb.2012.08.028. Epub 2012 Sep 7.
Maternal separation (MS) induces a series of changes in rats' behavior; among them a reduction in spontaneous sleep. One potentially impaired system is the endocannabinoid system (eCBs), since it contributes to generate sleep. To investigate if there are situations early in life that affect the eCBs, which would contribute to make rats vulnerable to suffering insomnia, we studied the rodent model of MS. Rats were separated from their mothers for 3h-periods daily, from postnatal day (PND) 2 to PND 16. Once they gained 250g of body weight (adult rats), they were implanted with electrodes to record the sleep-waking cycle (SWC). MS rats and non-MS (NMS) siblings were assigned to one of the following groups: vehicle, oleamide (OLE, an agonist of the cannabinoid receptor 1, CB1R), OLE+AM251 (an antagonist of the CB1R) and AM251 alone. Expression of the CBR1 receptor was also analyzed in the frontal cortex (FCx) and in the hippocampus (HIP) of both NMS and MS rats. Results indicated that MS induced a reduction in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep with the consequent increase in waking (W) as compared to NMS siblings. OLE normalized the SWC, and AM251 blocked such an effect. CB1R expression was reduced in the FCx and in the HIP of MS rats. Our results indicate that MS reduces sleep and CB1R expression and OLE improves sleep in adult rats.
母体分离（MS）会引起大鼠行为的一系列变化；其中包括自发性睡眠减少。一个可能受损的系统是内源性大麻素系统（eCBs），因为它有助于产生睡眠。为了研究生命早期是否有影响 eCBs 的情况，这将导致大鼠易患失眠，我们研究了 MS 的啮齿动物模型。大鼠从出生后第 2 天（PND2）到第 16 天（PND16）每天接受 3 小时的分离。一旦它们体重达到 250g（成年大鼠），就会植入电极以记录睡眠-觉醒周期（SWC）。MS 大鼠和非-MS（NMS）同胞被分配到以下组之一：载体、油酸酰胺（OLE，大麻素受体 1（CB1R）的激动剂）、OLE+AM251（CB1R 的拮抗剂）和单独的 AM251。还分析了 NMS 和 MS 大鼠的额皮质（FCx）和海马（HIP）中 CBR1 受体的表达。结果表明，与 NMS 同胞相比，MS 诱导非快速眼动（NREM）和快速眼动（REM）睡眠减少，同时清醒（W）增加。OLE 使 SWC 正常化，而 AM251 阻断了这种作用。MS 大鼠的 FCx 和 HIP 中 CB1R 表达减少。我们的结果表明，MS 减少了睡眠和 CB1R 表达，而 OLE 改善了成年大鼠的睡眠。
