Involvement of delta-and mu-opioid receptors in the delayed cerebral ischemic tolerance induced by repeated electroacupuncture preconditioning in rats.
BACKGROUND
Preconditioning with repeated electroacupuncture (EA) could mimic ischemic preconditioning to induce cerebral ischemic tolerance in rats. The present study was designed to investigate whether mu (micro)-, delta (delta)- or kappa (kappa)-opioid receptors are involved in the neuroprotection induced by repeated EA preconditioning.


METHODS
The rats were pretreated with naltrindole (NTI), nor-binaltorphimine (nor-BNI) or D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), which is a highly selective delta-, kappa- or micro-opioid receptor antagonist respectively, before each EA preconditioning (30 minutes per day, 5 days). Twenty-four hours after the last EA treatment, the middle cerebral artery occlusion (MCAO) was induced for 120 minutes. The brain infarct volume was determined with 2, 3, 5-triphenyltetrazolium chloride staining at 24 hours after MCAO and compared with that in rats which only received EA preconditioning. In another experiment, the met-enkephalin-like immunoreactivity in rat brain was investigated by immunohistochemistry in both EA preconditioning and control rats.


RESULTS
The EA preconditioning reduced brain infarct volume compared with the control rats (P = 0.000). Administration of both NTI and CTOP attenuated the brain infarct volume reduction induced by EA preconditioning, presenting with larger infarct volume than that in the EA preconditioning rats (P < 0.001). But nor-BNI administration did not block the infarct volume reduction induced by EA preconditioning, presenting with smaller infarct volume than the control group rats (P = 0.000). The number of met-enkephalin-like immunoreactivity positive neurons in the EA preconditioning rats was more than that of the control rats (P = 0.000).


CONCLUSIONS
Repeated EA preconditioning stimulates the release of enkephalins, which may bind delta- and micro-opioid receptors to induce the tolerance against focal cerebral ischemia.
Xiong
Li-ze
LZ
Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. lxiong@fmmu.edu.cn
Yang
Jing
J
Wang
Qiang
Q
Lu
Zhi-hong
ZH
D000818:Animals; D002545:Brain Ischemia / Q000517:prevention & control*; D015671:Electroacupuncture; D004744:Enkephalin, Methionine / Q000032:analysis; D007150:Immunohistochemistry; D019194:Ischemic Preconditioning; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000502:physiology*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology
D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; C051844:norbinaltorphimine; D013004:Somatostatin; D004744:Enkephalin, Methionine; D009271:Naltrexone; C055382:naltrindole