The effects of selective opioid antagonists on somatosensory evoked potentials during relative cerebral ischemia in rats.
Hemorrhagic hypotension in spontaneously hypertensive rats induces attenuation of somatosensory evoked potentials. In this model of relatively mild cerebral ischemia, our previous studies have shown that naloxone stereospecifically enhances the evoked potentials, without changes in cortical blood flow. The high dose of naloxone needed to enhance the evoked potentials suggests that the attenuation is mediated by low affinity opioid receptors (delta or kappa). In the present study, we used this model to study the effects of naloxone-methobromide (5 mg kg-1, a quaternary derivative of naloxone with selective peripheral action when injected intravenously), MR 2266 (1 mg kg-1, a kappa receptor antagonist), and naloxone (5 mg kg-1) as well as saline injection (as control) in four different groups of rats. Following injection, we examined the changes in somatosensory evoked potentials, cortical blood flow and heart rate for 15 min while mean arterial pressure was held constant by a pressure-regulating reservoir. Only naloxone changed the somatosensory evoked potential amplitude significantly compared with the saline group in which no effect was seen. However, there was a tendency for a delayed effect of naloxone-methobromide on the evoked potentials, possibly indicating that the substance slowly passes the blood-brain barrier. Naloxone and MR 2266 caused a transient decrease in heart rate, while following naloxone-methobromide injection there was a slight increase in heart rate. Our results thus indicate that the beneficial effects of naloxone on somatosensory evoked potentials during relative cerebral ischemia may be centrally mediated by a non-kappa mechanism.
Gunnarsson
T
T
Department of Physiology, University of Iceland, Reykjavik.
Sigurdardottir
S
S
Hoffmann
P
P
Skarphedinsson
J O
JO
D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology*; D001783:Blood Flow Velocity; D002540:Cerebral Cortex / Q000098:blood supply; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D010111:Oxymorphone / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR
D001575:Benzomorphans; D009270:Naloxone; C027247:MR 2266; D010111:Oxymorphone