Castilho V M, Avanzi V, Brandão M L
Laboratório de Psicobiologia, FFCLRP, Ribeirão Preto, SP, Brazil.
Pharmacol Biochem Behav. 1999 Mar;62(3):425-31. doi: 10.1016/s0091-3057(98)00197-x.
We have shown that the inferior colliculus is involved in the integration of defensive reactions. Electrical and chemical stimulation of this structure elicits fear and escape behavior, expressed respectively by immobility (freezing) and wild running, followed by jumps. In this study, we analyzed whether the defensive behavior integrated at this level of the midbrain tectum is also followed by antinociception and its chemical mediation. In addition, we further addressed whether or not the aversive states and the stress-induced analgesia share the same neural substrates in the inferior colliculus. To this end, animals chronically implanted with a chemitrode, an electrode glued to a guide cannula, in the inferior colliculus were injected with naltrexone, methysergide, ketanserin, and midazolam. The animals were submitted to gradual increases in the electrical stimulation of the inferior colliculus, which allowed the measurement of the thresholds for aversive responses--vigilance, freezing, and escape. Following the induction of the aversive behavioral responses the animals were submitted to the tail-flick test. The results obtained show that midazolam was the only treatment that changed the aversive thresholds. On the other hand, while naltrexone and midazolam did not affect the fear-induced analgesia, it was inhibited by microinjections of the serotonergic blockers, methysergide and ketanserin. These results emphasize previous data demonstrating the nonopioid nature of the unconditioned analgesia to brain-aversive stimulation. Because methysergide is a nonspecific antagonist of 5-HT receptors, and ketanserin acts with a high degree of specificity at 5-HT2/5-HT1C receptors, the present results suggest that activation of 5-HT2/5-HT1C receptors may be implicated in the antinociception induced by stimulation of the inferior colliculus. Moreover, the present data also indicate that aversive reactions and analgesia from inferior colliculus stimulation can be pharmacologically dissociated.
我们已经表明,下丘参与防御反应的整合。对该结构进行电刺激和化学刺激分别会引发恐惧和逃避行为,表现为静止不动(僵住)和疯狂奔跑,随后跳跃。在本研究中,我们分析了在中脑顶盖这一水平整合的防御行为是否也伴随着抗伤害感受及其化学介导作用。此外,我们进一步探讨了厌恶状态和应激诱导的镇痛在下丘中是否共享相同的神经底物。为此,向下丘中慢性植入化学电极(一种粘在引导套管上的电极)的动物注射纳曲酮、麦角新碱、酮色林和咪达唑仑。让动物接受下丘电刺激的逐渐增强,这使得能够测量厌恶反应(警觉、僵住和逃避)的阈值。在诱发厌恶行为反应后,对动物进行甩尾试验。获得的结果表明,咪达唑仑是唯一改变厌恶阈值的处理。另一方面,虽然纳曲酮和咪达唑仑不影响恐惧诱导的镇痛,但5-羟色胺能阻滞剂麦角新碱和酮色林的微量注射会抑制这种镇痛。这些结果强调了先前的数据,这些数据证明了对脑厌恶刺激的非阿片类无条件镇痛的性质。由于麦角新碱是5-羟色胺受体的非特异性拮抗剂,而酮色林对5-HT2/5-HT1C受体具有高度特异性作用,目前的结果表明5-HT2/5-HT1C受体的激活可能与下丘刺激诱导的抗伤害感受有关。此外,目前的数据还表明,下丘刺激引起的厌恶反应和镇痛在药理学上是可分离的。