Extended methamphetamine self-administration enhances reinstatement of drug seeking and impairs novel object recognition in rats
Extended methamphetamine self-administration enhances reinstatement of drug seeking and impairs novel object recognition in rats
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DOI：
10.1007/s00213-008-1187-7
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发表时间：
2008-09-01
影响因子：
3.4
通讯作者：
See, R. E.
中科院分区：
文献类型：
--
作者：
Rogers, J. L.;De Santis, S.;See, R. E.
理由：甲基苯丙胺是一种高度成瘾性的精神兴奋剂，长期使用甲基苯丙胺的人复发率很高。此外，长期滥用甲基苯丙胺可导致精神症状，并与各种认知功能障碍有关。然而，自我给药甲基苯丙胺对认知功能障碍和复发的影响尚未在动物模型中同时进行检查。目的：本研究确定短期和长期偶然获取甲基苯丙胺对自我给药、消退反应、甲基苯丙胺寻找恢复和客体探索任务认知表现的影响。材料与方法Long-Evans大鼠在每天1或2小时内自行静脉注射冰毒（0.02 mg/次）或生理盐水，连续10天，然后维持短时间（1或2小时）或长时间（6小时）自我给药，持续14天。杠杆反应在恢复之前被熄灭，恢复包括提供药物配对线索或启动注射甲基苯丙胺（1.0 mg/kg）。在自我给药前和停止自我给药后10-12天，还对动物进行了对象探索任务测试，从而比较了甲基苯丙胺暴露前和暴露后的情况。结果长期服用甲基苯丙胺导致每日摄入量增加。此外，短期和长期接触组的动物都表现出强大的条件提示和药物启动恢复，长期接触导致甲基苯丙胺启动恢复增强。自我服用甲基苯丙胺也会导致对新物体识别的接近依赖性损伤，但不会损害对空间重构的识别。结论长期自我服用甲基苯丙胺可增强药物启动恢复，降低新物体识别，表明长期偶然服用甲基苯丙胺可增加戒断后寻求药物的动机，同时增加认知缺陷。
Rationale Methamphetamine is a highly addictive psychostimulant, and chronic methamphetamine users show high rates of relapse. Furthermore, prolonged methamphetamine abuse can lead to psychiatric symptoms and has been associated with various cognitive dysfunctions. However, the impact of self-administered methamphetamine on cognitive dysfunction and relapse has not been concurrently examined in an animal model.Objectives The present study determined the effects of short- vs. long-access contingent methamphetamine on self-administration, extinction responding, reinstatement of methamphetamine seeking, and cognitive performance on an object exploration task.Materials and methods Long-Evans rats self-administered methamphetamine i.v. (0.02 mg/infusion) or received saline during daily sessions (1 or 2 h) for 10 days, followed by either maintained short- (1 or 2 h) or long-access (6 h) self-administration for 14 days. Lever responding was extinguished prior to reinstatement, which consisted of presentation of drug-paired cues or a priming injection of methamphetamine (1.0 mg/kg). Animals were also tested on an object exploration task prior to self-administration and at 10-12 days after cessation of self-administration, thus providing a comparison of pre-methamphetamine exposure with post-methamphetamine exposure.Results Long-access methamphetamine self-administration resulted in escalation of daily intake. Furthermore, animals in both short- and long-access groups showed robust conditioned-cued and drug-primed reinstatement, with long access resulting in enhanced methamphetamine-primed reinstatement. Methamphetamine self-administration also led to access-dependent impairments on novel object recognition but failed to impair recognition of spatial reconfiguration.Conclusions Extended methamphetamine self-administration enhances drug-primed reinstatement and decreases novel object recognition, indicating that prolonged contingent methamphetamine increases motivation for drug seeking following withdrawal while increasing cognitive deficits.