eCAM Advance Access published online on September 3, 2009
eCAM, doi:10.1093/ecam/nep132
Endogenous Opiates in the Nucleus Tractus Solitarius Mediate Electroacupuncture-induced Sleep Activities in Rats
1Department of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei 106, 2Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli and 3Graduate Institute of Acupuncture Science, College of Chinese Medicine, China Medical University, Taichung, Taiwan, ROC
Electroacupuncture (EA) possesses various therapeutic effects, including alleviation of pain, reduction of inflammation and improvement of sleep disturbance. The mechanisms of EA on sleep improvement, however, remain to be determined. It has been stated in ancient Chinese literature that the Anmian (EX17) acupoint is one of the trigger points that alleviates insomnia. We previously demonstrated that EA stimulation of Anmian acupoints in rats during the dark period enhances non-rapid eye movement (NREM) sleep, which involves the induction of cholinergic activity in the nucleus tractus solitarius (NTS). In addition to cholinergic activation of the NTS, activation of the endogenous opioidergic system may also be a mechanism by which acupuncture affects sleep. Therefore, this study was designed to investigate the involvement of the NTS opioidergic system in EA-induced alterations in sleep. Our present results indicate that EA of Anmian acupoints increased NREM sleep, but not rapid eye movement sleep, during the dark period in rats. This enhancement in NREM sleep was dose-dependently blocked by microinjection of opioid receptor antagonist, naloxone, and the µ-opioid receptor antagonist, naloxonazine, into the NTS; administrations of
-receptor antagonist, natrindole, and the
-receptor antagonist, nor-binaltrophimine, however, did not affect EA-induced alterations in sleep. Furthermore, β-endorphin was significantly increased in both the brainstem and hippocampus after the EA stimuli, an effect blocked by administration of the muscarinic antagonist scopolamine into the NTS. Our findings suggest that mechanisms of EA-induced NREM sleep enhancement may be mediated, in part, by cholinergic activation, stimulation of the opiodergic neurons to increase the concentrations of β-endorphin and the involvement of the µ-opioid receptors.
Keywords: electroacupuncture – β-endorphin – nucleus tractus solitarius (NTS) – µ-opioid receptor – sleep
For reprints and all correspondence: Fang-Chia Chang, Department of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, No. 1, Sec. 4., Roosevelt Road, Taipei 106, Taiwan, ROC. Tel: +886-2-3366-3883; Fax: +886-2-2366-1475; E-mail: fchang{at}ntu.edu.tw
*These authors contribute equally to this work.
Received March 26, 2009; accepted August 6, 2009