Reversal of induced ischemic neurologic deficit in gerbils by the opiate antagonist naloxone

Microsurgical unilateral occlusion of the right common carotid artery in 140 adult male gerbils produced homolateral cerebral ischemia and a neurologic deficit (stroke) in 42 percent (group A); the other 58 percent did not develop signs of stroke (group B). Intraperitoneal injection of the opiate antagonist naloxone (1 milligram per kilogram of body weight) reversed the signs of stroke within 3 to 5 minutes in ten out of ten group A gerbils; the effect lasted up to 30 minutes, after which stroke returned. Repeated injections of naloxone reversed stroke, but all ten gerbils died within 48 hours of ligation. However, nine other group A gerbils implanted with 10-milligram naloxone pellets had continuous reversal of signs of stroke, and four survived for more than 2 weeks. Twenty-one out of 24 group B gerbils injected intraperitoneally with morphine sulfate (5 to 30 milligrams per kilogram) 9 hours after ligation developed stroke within 3 to 20 minutes; morphine-induced stroke lasted 4 to 24 hours and could be reversed by intraperitoneal injection of naloxone. Ten out of 11 other group B gerbils injected intraperitoneally with the stereoisomeric opiate agonist levorphanol 9 hours after ligation developed signs of mild stroke that were reversed by intraperitoneal injection of naloxone. Ten other group B gerbils injected intraperitoneally with dextrorphan, the inactive enantiomer of levorphanol, 9 hours after ligation did not develop signs of stroke. Intraperitoneal injection of an enkephalin analog (Sandoz FK33824; 15 milligrams per kilogram) 9 hours after ligation did not produce stroke in ten other group B gerbils. These findings suggest the involvement of endorphins and opiate receptors in the pathophysiology of stroke and suggest the possible clinical use of opiate antagonists in humans in the acute phase of stroke.