CP 55,940 (CP) provides protection from ischemic damage due to middle cerebral artery occlusion (MCAO) via the cannabinoid (CB) 1 receptor

Stimulation of CB receptors by WIN 55,212‐2 provides neuroprotection during cerebral ischemia. The present study was undertaken to determine if CP provides similar protection by stimulating the CB 1 receptor. Male Sprague‐Dawley rats were divided into 5 groups: 3 groups underwent reversible MCAO using an intraluminal suture; 1 group underwent sham surgery; 1 group served as non‐surgical control. Rats were anesthetized and surgically prepared for MCAO and iv drug administration. The suture was advanced until resistance felt to induce stroke. Rats were given a bolus of AM 251 (AM; 3.0 mg/kg, iv) or vehicle 2.5 h into occlusion. Thirty min later (3 h into occlusion) the rats were given CP (0.3 mg/kg, iv) or vehicle. The suture was withdrawn 3.5 h into occlusion and CP infused (0.9 mg/kg/hr, iv) over the next 5 h. Rats were killed 72 h later, and their brains removed, frozen, and stained for analyzing by image J software. CP reduced the percent infarct volume of the total brain (12.7 ± 2.2 % versus 33.5 ± 6.0 % in the MCAO group; P<0.001). AM 251 prevented the protective effect of CP (39.6 ± 3.5 %; P<0.001 compared to CP and control groups). AM 251 alone increased ischemia (57.6 ± 8.5 %; P<0.001 compared to CP and P<0.05 compared to CP+AM groups). CP provides neuroprotection by stimulation of the CB 1 receptor. Supported by a KCOM Graduate Program Grant.