Reversal of Induced Ischemic Neurologic Deficit in Gerbils by the Opiate Antagonist Naloxone

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Abstract
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% (group A); the other 58% did not develop signs of stroke (group B). I.p. injection of the opiate antagonist naloxone (1 mg/kg body wt) reversed the signs of stroke within 3-5 min in 10 out of 10 group A gerbils; the effect lasted up to 30 min, after which stroke returned. Repeated injections of naloxone reversed stroke, but all 10 gerbils died within 48 h of ligation. However, 9 other group A gerbils implanted with 10 mg naloxone pellets had continuous reversal of signs of stroke, and 4 survived for more than 2 wk. A total of 21 of 24 group B gerbils injected i.p. with morphine sulfate (5-30 mg/kg) 9 h after ligation developed stroke within 3-20 min; morphine-induced stroke lasted 4-24 h and could be reversed by i.p. injection of naloxone. Ten out of 11 other group B gerbils injected i.p. with the stereoisomeric opiate agonist levorphanol 9 h after ligation developed signs of mild stroke that were reversed by i.p. injection of naloxone. Ten other group B gerbils injected i.p. with dextrorphan, the inactive enantiomer of levorphanol, 9 h after ligation did not develop signs of stroke. I.p. injection of an enkephalin analog (FK33824 [(D-Ala2,MePhe4,Met(O)5-ol)enkephalin] 15 mg/kg) 9 h after ligation did not produce stroke in 10 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.