Involvement of cannabinoid receptor 1 in ischemic tolerance induced by pre-treatment with repeated electroacu-puncture in rats
AIM: To explore whether cannabinoid receptor 1 (CB1) participates in the ischemic tolerance induced by pretreatment with repeated electroacupuncture. METHODS: Forty-eight male SD rats were randomly assigned to 6 groups (n = 8 in each group): Sham group, control (Con) group, electroacupuncture (EA) group, vehicle plus electroacupuncture (v-EA) group, CB1 receptor antagonist (AM) group and CB1 receptor antagonist plus electroacupuncture (AM-EA) group. All the animals were anesthetized with intraperitoneal injection of 40 mg/kg pentobarbital sodium once a day for 5 consecutive days except those in Sham group. Rats in Sham group only received sham operation, rats in Con group were only subjected to ischemia and reperfusion, rats in EA group received electroacupuncture at the Baihui acupoint for 30 min a day for 5 consecutive days, rats in AM group received AM251 1 mg/kg (ip) once a day for 5 consecutive days, and rats in v-EA group and AM-EA group received electroacupuncture at the Baihui acupoint for 30 min and were respectively injected with vehicle (DMSO:Tween-80:saline = 1:1:8) 3 mL/kg and AM251 1 mg/kg (ip) 30 min prior to the onset of electroacupunuture once a day for 5 consecutive days. Twenty-four hours after last treatment, all groups except Sham group received the middle cerebral artery occlusion. The neurological function scores (NFS) of all the rats were evaluated at 24 h after reperfusion. The brain infarct volume, as a percentage of volume at normal cerebral hemisphere, was then assessed by 2, 3, 5 triphenyltetrazolium chloride (TTC) staining after the evaluation of NFS. RESULTS: In Sham group, no neurological deficits and infarct volume were observed. The NFS in EA group and v-EA group were significantly higher than that in Con group, AM group and AM-EA group (P < 0.05). The infarct volume percentage in EA group and v-EA group was (31.4 ± 8.3)% and (27.2 ± 9.3)%, which was significantly smaller than that in Con group, AM group and AM-EA group (P < 0.05). No significant difference was observed between AM group, AM-EA group and Con group. CONCLUSION: The ischemic tolerance induced by pretreatment with repeated electroacupuncture in rats is possibly via the activation of the CB1 receptor in the brain.