Peptides, Vol. 10, pp. 493--497. ©Pergamon Press plc, 1989. Printed in the U.S.A. 0196-9781/89 $3.00 + .00 Differential Inhibitory Effects of MIF-1, Tyr-MIF-1, Naloxone and [3-Funaltrexamine on Body Rotation-Induced Analgesia in the Meadow Vole, Microtus pennsylvanicus SUSAN M. LIPA, MARTIN KAVALIERS l AND KLAUS-PETER OSSENKOPP Division of Oral Biology, Faculty of Dentistry, and Department of Psychology The University of Western Ontario, London, Ontario Canada N6A 5C1 Received 21 December 1988 LIPA, S. M., M. KAVALIERS AND K.-P. OSSENKOPP. Differential inhibitory effects of MIF-1, Tyr-MIF-I, naloxone and f~-funaltrexamine on body rotation-induced analgesia in the meadow vole, Microtus pennsylvanicus. PEPTIDES 10(3) 493- 497, 1989.--The effects of body rotation in a horizontal plane and various opiate antagonists on the nociceptive responses of a day-active microtine rodent, the meadow vole, Microtuspennsylvanicus, were examined. Intermittent rotation (70 rpm, schedule of 30 sec on, 30 sec off) for 30 min induced significant analgesic responses in the voles for 15 min after rotation. These increases in thermal response latency were blocked by intraperitoneal pretreatment with either naloxone or the irreversible mu opiate receptor antagonist [3-funaltrexamine ([3-FNA; 10 mg/kg; 24 hr pretreatment). This antagonistic effect of 13-FNA indicates mu opioid involvement in the mediation of rotation-induced analgesia. The antiopiate peptides MIF-1 (Pro-Leu-Gly-NH2) and Tyr-MIF-1 also significantly reduced, though did not completely block, body rotation-induced opiate analgesia. This suggests that Tyr-MIF-1 and MIF-1 have significant antagonistic effects on mu opioid systems that are involved in the mediation of stress (rotation)-induced analgesia. Body rotation Stress-induced analgesia Mu opioid [3-Funaltrexamine Naloxone MIF-1 Tyr-MIF-I Meadow vole A broad range of stimuli is capable of activating endogenous analgesic mechanisms and rendering animals less responsive to aversive stimuli. Stress-, or more appropriately, environmentally- induced analgesia, has been observed in laboratory rodents ex- posed to stimuli such as foot-shock, warm- and cold-water swim, immobilization, body or tail pinch and centrifugal rotation (3, 12, 17, 21). Moreover, depending on the characteristics of the stressful stimuli (e.g., duration, intensity, temporal patterning), the analgesia may be mediated by either endogenous opioid systems or nonopioid hormonal and neurochemical mechanisms (3). For example, results of studies of the effects of centrifugal rotation (vestibular stimulation plus restraint stress) have revealed the induction of opioid analgesia at slow (110 rpm) rotation speeds (4) and nonopioid analgesia at high speeds (4,7). Body rotation per se has also been found to be a stressor in studies with laboratory rodents. Evidence for the stressful nature of body rotation includes: postrotatory reductions in activity (8) and feeding and drinking (8, 9, 14, 28), as well as increases in defecation levels in rats (27). Measurements of hormonal and behavioral changes in motion-sick individuals subjected to body rotation have confirmed the aversive nature of the rotation- associated vestibular stimulation (33). Results of recent studies with laboratory mice, Mus musculus, showed that body rotation in a horizontal plane can also induce significant analgesic responses (29,30). Moreover, in contrast to the opioid-nonopioid dichotomy observed with other stressors (3), a variety of different schedules of rotation (duration, temporal patterning) were all observed to induce an analgesia that was sensitive to the prototypic opiate antagonist naloxone (29,30). This suggests that body rotation may be a useful stressor for inducing opioid-mediated analgesia. However, investigations with additional species, and opiate antag- onists other than naloxone, are necessary before any definite conclusions about the effects of body rotation on opioid activation can be drawn. At least three distinct types of opioid receptors, ~, n and 8, are proposed to exist. Studies with selective opiate antagonists have shown that antinociception can be mediated via Ix and to a lesser extent K receptors, with the roles of 8 receptors being more controversial (2, 16, 35). Naloxone, although having the highest affinity for I~ receptors, also binds readily to other categories of 1Requests for reprints should be addressed to M. Kavaliers, Division of Oral Biology, Faculty of Dentistry, The University of Western Ontario, London, Ontario Canada N6A 5C1. 493