Dalley Jeffrey W, Theobald David E H, Berry David, Milstein Jean A, Lääne Kristjan, Everitt Barry J, Robbins Trevor W
Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge, UK.
Neuropsychopharmacology. 2005 Mar;30(3):525-37. doi: 10.1038/sj.npp.1300590.
Characterizing the nature and severity of cognitive deficits associated with chronic stimulant abuse may provide new insights into the neural substrates of drug addiction because such deficits may contribute to the chronic relapsing nature of compulsive drug use. This investigation examines in rats the long-term cognitive consequences of intravenously self-administered amphetamine, specifically on performance of a 5-choice serial reaction time task (5-CSRTT), which assesses visuo-spatial attention and impulsivity. Rats experienced 5 days of intravenous (i.v.) amphetamine self-administration and were then withdrawn for a period of 9 days, during which time testing on the 5-CSRTT took place. This was repeated on five consecutive occasions for a period of 10 weeks. Controls experienced identical training on the 5-CSRTT but during the self-administration sessions received yoked i.v. infusions of normal saline. The results reveal a selective and reproducible pattern of deficits on the 5-CSRTT following repeated withdrawal from amphetamine self-administration, with deleterious effects on the speed and accuracy of responding as well as increased omission errors. Premature (impulsive) responding, perseveration, and food consumption latencies were not significantly affected. Deficits in attentional performance fully recovered 4-5 days after amphetamine cessation and there was no evidence of any long-term disturbances, even when the attentional load was increased. However, following a 2-month abstinence period, abnormalities in the subsequent effects of acute noncontingent amphetamine were found, with increased omissions, slower response times, and reduced impulsivity. Thus, contingent i.v. amphetamine administration has both short- and long-term consequences, which may be relevant to the complex disturbances that accompany drug addiction.
明确与慢性兴奋剂滥用相关的认知缺陷的性质和严重程度，可能会为药物成瘾的神经基础提供新的见解，因为这些缺陷可能导致强迫性药物使用的慢性复发性。本研究在大鼠中检测静脉注射自我给药苯丙胺的长期认知后果，特别是对5选串行反应时任务（5-CSRTT）表现的影响，该任务评估视觉空间注意力和冲动性。大鼠经历5天的静脉注射苯丙胺自我给药，然后停药9天，在此期间进行5-CSRTT测试。连续5次重复此过程，为期10周。对照组在5-CSRTT上接受相同的训练，但在自我给药期间接受配对的静脉注射生理盐水。结果显示，在反复停止苯丙胺自我给药后，5-CSRTT上存在选择性和可重复的缺陷模式，对反应速度和准确性有有害影响，同时遗漏错误增加。过早（冲动）反应、持续性和食物摄取潜伏期未受到显著影响。注意力表现的缺陷在苯丙胺戒断后4-5天完全恢复，即使注意力负荷增加，也没有任何长期干扰的证据。然而，在2个月的禁欲期后，发现急性非条件性苯丙胺的后续效应存在异常，遗漏增加、反应时间变慢和冲动性降低。因此，静脉注射苯丙胺给药有短期和长期后果，这可能与药物成瘾伴随的复杂干扰有关。
