Preserving and restoring behavioral potential within the spinal cord using an instrumental training paradigm
Preserving and restoring behavioral potential within the spinal cord using an instrumental training paradigm
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DOI：
10.1152/jn.2001.86.2.845
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发表时间：
2001-08-01
影响因子：
2.5
通讯作者：
Grau, JW
中科院分区：
文献类型：
--
作者：
Crown, ED;Grau, JW
我们已经证明，脊髓神经元可以支持一种简单的工具性学习。在一个典型的实验中，大鼠在第二胸椎(T-2)棘化，并对一条后腿进行电击。当腿伸展时，一组(主人)会受到电击。这种应激反应会导致反应持续时间的增加，从而减少净电击暴露。这种工具性学习在接受与腿部位置无关的等量电击(非或有电击)的带轭对照组中没有观察到。有趣的是，接受非应然电击的大鼠也无法学习，当它们随后暴露在同侧或对侧腿上的应激反应应激时。只要对腿或尾巴施加6分钟的非偶然伤害性刺激，就会破坏长达48小时的行为潜力。本实验探索行为疗法是否可以预防和/或逆转这一缺陷。在实验1中，脊髓化的大鼠接受了30分钟的有或有休克、非或有休克或在非或有尾部休克之前不进行任何训练。然后对他们的对侧后腿进行或有电击测试。单独接受非偶然电击的大鼠无法学习。事先暴露在或有休克中具有预防赤字的免疫效果。实验2考察了在非或有电击暴露后进行或有电击训练是否能恢复行为潜能。为了促进应急休克训练期间的表现，受试者被给予鞘内注射阿片类拮抗剂纳曲酮，这是一种暂时阻止行为缺陷表达的药物治疗。24小时后，受试者接受同侧或对侧腿部偶发休克的测试。我们发现纳曲酮联合或有休克治疗可以恢复脊髓功能。纳曲酮单独治疗无效。这些结果表明，非偶然伤害性刺激可以破坏脊髓损伤后的行为潜力，而工具性训练可以帮助保存和保护脊髓功能。
We have shown that spinal cord neurons can support a simple form of instrumental learning. In a typical experiment, rats are spinalized at the second thoracic vertebra (T-2) and given shock to one hindleg. One group (master) receives shock whenever the leg is extended. This response-contingent shock causes an increase in response duration that decreases net shock exposure. This instrumental learning is not observed in yoked controls that receive the same amount of shock independent of leg position (noncontingent shock). Interestingly, rats that have received noncontingent shock also fail to learn when they are subsequently exposed to response-contingent shock on either the ipsilateral or contralateral leg. Just 6 min of noncontingent nociceptive stimulation, applied to the leg or tail, undermines behavioral potential for up to 48 h. The present experiments explore whether a behavioral therapy can prevent and/or reverse this deficit. In experiment 1, spinalized rats received 30 min of training with contingent shock, noncontingent shock, or nothing prior to noncontingent tailshock. They were then tested with contingent shock to the contralateral hindleg. Rats that had received noncontingent shock alone failed to learn. Prior exposure to contingent shock had an immunizing effect that prevented the deficit. Experiment 2 examined whether training with contingent shock after noncontingent shock exposure would restore behavioral potential. To facilitate performance during contingent shock training, subjects were given an intrathecal injection of the opioid antagonist naltrexone, a drug treatment that temporarily blocks the expression of the behavioral deficit. Twenty-four hours later subjects were tested with contingent shock on either the ipsilateral or contralateral leg. We found that naltrexone combined with contingent shock therapy restored spinal cord function. Naltrexone alone had no effect. The results suggest that noncontingent nociceptive stimulation can undermine behavioral potential after spinal cord injury and that instrumental training can help preserve, and protect, spinal cord function.