Morgan M M, Whitney P K, Gold M S
Department of Psychology, Washington State University, 14204 NE Salmon Creek Ave., Vancouver, WA 98686, USA.
Brain Res. 1998 Aug 31;804(1):159-66. doi: 10.1016/s0006-8993(98)00669-6.
It has long been known that the periaqueductal gray (PAG) plays an important role in the modulation of nociception. Given that activation of the lateral PAG also produces wild running and tachycardia, it has been suggested that PAG mediated antinociception is part of an integrated defensive reaction. However, an alternative hypothesis is that these effects are merely a secondary response to aversive brain stimulation. If antinociception and flight reactions are caused by aversive brain stimulation, then these effects should always occur together. The objective of the present study was to determine whether antinociception and locomotion could be dissociated by microinjecting morphine and kainic acid into various subdivisions of the caudal PAG. Non-selective activation of lateral and dorsal regions of the PAG by microinjection of kainic acid produced wild running, while injections into the ventrolateral PAG produced immobility. Microinjection of morphine evoked similar locomotor effects, although the onset to effect was slower with morphine (approximately 5 min vs. 1 min for kainic acid), and the antinociceptive efficacy of microinjecting 0.2 microl of morphine was less than with kainic acid injections. In fact, microinjection of morphine evoked locomotor effects in the absence of antinociception on 39% of the tests. Increasing the injection volume to 0.4 microl (dose remained at 5 microg) greatly enhanced the likelihood that antinociception and locomotor effects (e.g. running, freezing, circling) occurred simultaneously (79%). These findings indicate that, although distinct locomotor effects are associated with antinociception from the ventral and more dorsal regions of the PAG, antinociceptive and locomotor effects can occur independently. This finding is consistent with the hypothesis that ventral and dorsal regions of the PAG integrate defensive freezing and flight reactions, respectively.
长期以来，人们一直知道中脑导水管周围灰质（PAG）在伤害感受调制中起重要作用。鉴于外侧PAG的激活也会产生狂奔和心动过速，有人提出PAG介导的抗伤害感受是综合防御反应的一部分。然而，另一种假设是，这些效应仅仅是对厌恶性脑刺激的次级反应。如果抗伤害感受和逃避反应是由厌恶性脑刺激引起的，那么这些效应应该总是同时出现。本研究的目的是通过向尾侧PAG的各个亚区微量注射吗啡和 kainic 酸来确定抗伤害感受和运动是否可以分离。微量注射 kainic 酸对PAG外侧和背侧区域的非选择性激活会产生狂奔，而注射到腹外侧PAG则会导致不动。微量注射吗啡会引起类似的运动效应，尽管吗啡的起效较慢（约5分钟，而 kainic 酸为1分钟），并且微量注射0.2微升吗啡的抗伤害感受效果不如注射 kainic 酸。事实上，在39%的测试中，微量注射吗啡在没有抗伤害感受的情况下引起了运动效应。将注射体积增加到0.4微升（剂量保持在5微克）大大增加了抗伤害感受和运动效应（如奔跑、僵住、转圈）同时出现的可能性（79%）。这些发现表明，尽管不同的运动效应与PAG腹侧和背侧区域的抗伤害感受相关，但抗伤害感受和运动效应可以独立发生。这一发现与PAG腹侧和背侧区域分别整合防御性僵住和逃避反应的假设一致。
