Stimulus-response functions of the lateral dorsal striatum and regulation of behavior studied in a cocaine maintenance/cue reinstatement model in rats
Stimulus-response functions of the lateral dorsal striatum and regulation of behavior studied in a cocaine maintenance/cue reinstatement model in rats
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DOI：
10.1007/s00213-002-1036-z
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发表时间：
2002-05-01
影响因子：
3.4
通讯作者：
Eichenbaum, HB
中科院分区：
文献类型：
--
作者：
Kantak, KM;Black, Y;Eichenbaum, HB
基本原理：为了研究潜在的神经认知机制的药物寻求和吸毒行为，可逆的利多卡因诱导的失活的侧背纹状体（DST）的药物维持/线索恢复模型中研究的行为的影响进行了评估。研究DST的这个区域是因为它选择性地调节刺激-反应学习，而10 μ g双侧输注的利多卡因会破坏这种学习。方法：大鼠（n=6）进行训练，以自我管理1 mg/kg/输注可卡因下的第二顺序的药物输送计划。双侧利多卡因（30-100 pg）灭活侧DST的影响进行了评价，在药物维持试验期间，以及在测试中，其中恢复可卡因相关的线索与可卡因引发注射相结合的反应。使用较低的10 μ g剂量来检查利多卡因对单独提示诱导的反应恢复的影响。结果：在药物维持试验中，100 μ g利多卡因灭活后，觅药行为显著增加。获得的输注次数没有变化。在可卡因引发注射之前的线索诱导恢复测试期间，100 μ g利多卡因显著降低了药物寻求行为和获得的输注配对光递送的数量。在恢复测试与线索单独提出，失活的横向DST 10微克利多卡因没有影响任何一个行为。结论：这些研究结果表明，刺激反应功能的横向DST可能会调节剂量相关的影响，自我管理的可卡因，因为利多卡因诱导的行为变化在维护和可卡因启动测试类似的影响，暴露于越来越低剂量的可卡因，分别。考虑到在单独线索测试期间缺乏利多卡因的作用，侧DST似乎本身并不调节药物寻求行为（即，当药物不可用时，由药物相关线索维持的反应）。
Rationale: To investigate potential neurocognitive mechanisms underlying drug-seeking and drug-taking behavior, the effects of reversible lidocaine-induced inactivation of the lateral dorsal striatum (DST) on behavior studied in a drug maintenance/cue reinstatement model were evaluated. This region of the DST was investigated because it selectively regulates stimulus-response learning that is disrupted by 10 mug of bilaterally infused lidocaine. Methods: Rats (n=6) were trained to self-administer 1 mg/kg per infusion cocaine under a second-order schedule of drug delivery. The effects of bilateral lidocaine (30-100 pg) inactivation of the lateral DST were evaluated during drug maintenance tests as well as during tests in which responding was reinstated by cocaine-associated cues presented in combination with a cocaine priming injection. The lower 10 mug dose was used to examine the effects of lidocaine on reinstatement of responding induced by presentation of cues alone. Results: During drug maintenance tests, drug-seeking behavior was significantly increased after inactivation by 100 mug lidocaine. The number of infusions earned did not change. During cue-induced reinstatement tests preceded by a cocaine priming injection, 100 mug lidocaine significantly decreased both drug-seeking behavior and the number of infusion-paired light deliveries earned. During reinstatement tests with cues presented alone, inactivation of the lateral DST by 10 mug lidocaine did not influence either behavior. Conclusions: These findings suggest that stimulus-response functions of the lateral DST may regulate the dose-related effects of self-administered cocaine because the lidocaine-induced changes in behavior during the maintenance and cocaine priming tests resembled the effects of exposure to increasingly lower doses of cocaine, respectively. Given the lack of an effect of lidocaine during the cues-alone tests, the lateral DST does not appear to regulate drug-seeking behavior per se (i.e., responding maintained by drug-associated cues at times when drug is not available).