Gunnarsson T, Sigurdardottir S, Hoffmann P, Skarphedinsson J O
Department of Physiology, University of Iceland, Reykjavik.
Life Sci. 1994;55(17):1365-74. doi: 10.1016/0024-3205(94)00769-1.
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.
自发性高血压大鼠的出血性低血压会导致体感诱发电位减弱。在这个相对轻度脑缺血的模型中，我们之前的研究表明，纳洛酮能立体特异性地增强诱发电位，而皮质血流无变化。增强诱发电位所需的高剂量纳洛酮表明，这种减弱是由低亲和力阿片受体（δ或κ）介导的。在本研究中，我们使用这个模型来研究纳洛酮甲溴化物（5毫克/千克，纳洛酮的一种季铵衍生物，静脉注射时有选择性外周作用）、MR 2266（1毫克/千克，一种κ受体拮抗剂）、纳洛酮（5毫克/千克）以及生理盐水注射（作为对照）对四组不同大鼠的影响。注射后，我们在通过压力调节贮液器使平均动脉压保持恒定的同时，检测了15分钟内体感诱发电位、皮质血流和心率的变化。与未见效果的生理盐水组相比，只有纳洛酮显著改变了体感诱发电位的幅度。然而，纳洛酮甲溴化物对诱发电位有延迟作用的趋势，这可能表明该物质缓慢通过血脑屏障。纳洛酮和MR 2266导致心率短暂下降，而注射纳洛酮甲溴化物后心率略有上升。因此，我们的结果表明，纳洛酮在相对脑缺血期间对体感诱发电位的有益作用可能由非κ机制中枢介导。
