Effects of direct periaqueductal grey administration of a cannabinoid receptor agonist on nociceptive and aversive responses in rats
Effects of direct periaqueductal grey administration of a cannabinoid receptor agonist on nociceptive and aversive responses in rats
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DOI：
10.1016/s0028-3908(03)00235-1
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发表时间：
2003-10-01
影响因子：
4.7
通讯作者：
Chapman, V
中科院分区：
文献类型：
--
作者：
Finn, DP;Jhaveri, MD;Chapman, V
大麻素的镇痛潜力可能会受到全身给药时产生厌恶情绪的能力的阻碍。我们研究了中脑导水管周围灰质（PAG）是介导大麻素抗伤害性和潜在厌恶作用的常见底物的假设。大鼠福尔马林试验用于模拟伤害感受行为。PAG内微量注射兴奋性氨基酸D，L-同型半胱氨酸（DLH）诱导一个厌恶的，恐慌样反应的防御性“战斗或逃跑”的反应特征。将大麻素受体激动剂HU 210（5 μ g/大鼠）施用到背侧PAG中显著降低了福尔马林诱发的伤害性行为的第二阶段，这种作用被CB 1受体拮抗剂SR 141716 A（50 μ g/大鼠）的共同施用所阻断。这种抗伤害性作用伴随着HU 210诱导的福尔马林诱导的尾侧PAG中Fos蛋白表达增加的衰减。背内PAG给药HU 210（0.1，1或5 μ g/大鼠）显着减少了厌恶DLH诱导的爆发性运动反应。HU 210的抗伤害性作用可能是由于下行抑制性疼痛通路的激活。介导PAG中大麻素抗厌恶作用的机制仍有待阐明。这些数据暗示了PAG在大麻素介导的抗伤害性和抗厌恶反应中的作用。(C)2003爱思唯尔有限公司。保留所有权利。
The analgesic potential of cannabinoids may be hampered by their ability to produce aversive emotion when administered systemically. We investigated the hypothesis that the midbrain periaqueductal grey (PAG) is a common substrate mediating the anti-nociceptive and potential aversive effects of cannabinoids. The rat formalin test was used to model nociceptive behaviour. Intra-PAG microinjection of the excitatory amino acid D,L-homocysteic acid (DLH) was used to induce an aversive, panic-like reaction characteristic of the defensive "fight or flight" response. Administration of the cannabinoid receptor agonist HU210 (5 mug/rat) into the dorsal PAG significantly reduced the second phase of formalin-evoked nociceptive behaviour, an effect which was blocked by co-administration of the CB1 receptor antagonist SR141716A (50 mug/rat). This anti-nociceptive effect was accompanied by an HU210-induced attenuation of the formalin-evoked increase in Fos protein expression in the caudal lateral PAG. Intra-dorsal PAG administration of HU210 (0.1, 1 or 5 mug/rat) significantly reduced the aversive DLH-induced explosive locomotor response. The anti-nociceptive effect of HU210 is likely to result from activation of the descending inhibitory pain pathway. Mechanisms mediating the anti-aversive effects of cannabinoids in the PAG remain to be elucidated. These data implicate a role for the PAG in both cannabinoid-mediated anti-nociceptive and anti-aversive responses. (C) 2003 Elsevier Ltd. All rights reserved.