2006-08-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/696630摘要：我們先前的研究顯示：電針刺激安眠穴能增加老鼠在黑暗期 (活動期) 的睡眠；在黑暗期前給予一次二十分鐘的電針刺激安眠穴能增加快速動眼期睡眠 (rapid eye movement sleep; REMS)，但對於非快速動眼期睡眠 (non-REM sleep; NREMS) 並無影響；當連續兩天的黑暗期前給予二十分鐘電針刺激發現: REMS 和NREMS均有明顯的增加；而偽電針刺激非穴位對睡眠並無影響。這些結果顯示電針刺激安眠穴的確會調節老鼠的睡眠。早先的結果亦顯示：當周邊腹腔給予muscarinic 受體拮抗劑能有效的抑制電針刺激安眠穴所增加的睡眠；另外當電燒破壞掉caudal nucleus tractus solitarius (NTS) 後，電針刺激安眠穴就無法對睡眠有所影響；若只有腹腔給予muscarinic 受體拮抗劑 (無電針刺激安眠穴) 會增加老鼠的睡眠；而單純的電燒破壞掉caudal NTS (無電針刺激安眠穴) 對睡眠則無影響。根據這些研究成果我們假設：電針刺激安眠穴增加老鼠在黑暗期的睡眠可能是透過興奮迷走神經進而刺激caudal NTS中的muscarinic 受體<br> Abstract: Electroacupuncture (EAc) possesses a broad therapeutic effect, including improvement of sleep disturbance. The mechanism of sleep improvement of EAc, however, is still unclear. Our previous study showed the effects of EAc stimulation of “Anmian (extra)” acupoints on sleep alteration and the implication of a plausibly active structure, the caudal nucleus tractus solitarius (NTS). Previous results have shown that rapid eye movement sleep (REMS) was enhanced during the dark period when a single EAc stimulation was given 25 minutes prior to the onset of the dark period. REMS and slow wave sleep (SWS) increased during the dark period after administration of EAc stimuli on two consecutive days. Electrical stimulation of non-acupoints produced no change in the sleep pattern. Pharmacological blockade of muscarinic cholinergic receptors by systemic administration of scopolamine dose-dependently attenuated EAc-induced disruptions in REMS and SWS. Furthermore, electrical lesions in the bilateral caudal NTS produced significant blockade of EAc-induced sleep enhancement. However, in rats without EAc, scopolamine increased SWS during the dark period, but caudal NTS lesions did not alter sleep. These results suggest that the caudal NTS may be involved in the regulation of EAc-induced sleep alterations. It has been reported that EAc increases beta-endorphin in hypothalamus and caudal NTS. Microinjection of morphine into the NTS provokes a dose-dependent enhancement of all the polygraphic and behavioral manifestations of SWS and this effect is blocked by naloxone, suggesting that endogenous opioid is involved in controlling electrocortical activity, such as SWS, generated by the NTS. Furthermore, it has been documented that vagal afferents activate the beta-endorphin system in the NTS, which in turn mediates mechanisms in response to vagal activation. Based upon our previous results and aforementioned evidence, the effects of EAc on sleep regulation could be mediated by activation of caudal NTS neurons via muscarinic receptors directly or via a cholinergic receptor-mediated increase of beta-endorphin concentrations in the caudal NTS. The current proposal is designed to elucidate above questions. In the first-year proposal, we will (1) microinject broad spectrum opioid antagonis, naloxone into caudal NTS with EAc at “Anmain” to delineate the role of-endorphin in EAc effect, (2) microinject opioid mu, delta and kapa antagonists, naloxonazine, natrindole and nor-binaltorphimine, respectively, into caudal NTS to further elucidate the involvement of specific opioid receptor subtypes, (3) microinject muscarinic receptor antagonist scopolamine into caudal NTS to further prove the role of muscarinic receptors in caudal NTS on the EAc effect, EAc at “Anmain” and determine the expression of beta-endorphin in brainstem to direct elucidate the involvement of beta-endorphin, and (4) microinject scopolamine into caudal NTS with EAc to determine the alteration of beta-endorphelectroacupunctureendorphinNTSsleepelectroacupunctureendorphinNTSsleep