Slezak Jonathan M, Katz Jonathan L
Psychobiology Section, Molecular Targets and Medications Discovery Research Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health.
Exp Clin Psychopharmacol. 2013 Oct;21(5):355-62. doi: 10.1037/a0033726.
The five-choice serial reaction time (5-CSRT) procedure has been considered a translational tool for assessments of the psychopharmacology of attention in preclinical research. Because greater sensitivity to delayed reinforcement may promote the development of attention-deficit/hyperactivity disorder (ADHD) symptoms, effects of reinforcer delay and psychostimulants on performances under a 5-CSRT procedure were determined. Male rats were trained to respond under a 5-CSRT procedure with different delay-of-reinforcement conditions (0, 2, 4, 8, 16 s), and effects of d-amphetamine, methylphenidate, and morphine (as a negative control) were assessed at 0- and 16-s delays. Under nondrug conditions, as the delay increased both response latency and the number of trials in which a response did not occur (omissions) increased, and the percent correct on trials when responses were emitted decreased. Only modest increases in the percent correct were found with psychostimulants during the 0-s delay condition; however, more substantial enhancements were found with a 16-s delay. Consistent effects of both psychostimulants at either delay on omissions and response latency were not observed. Morphine increased omissions and response latency at both delays and decreased the percent correct (16-s delay). Generally, responses during the intertrial interval were not systematically affected under any condition. The current results demonstrate that measures of attention in a 5-CSRT procedure are sensitive to changes in the delay to reinforcer delivery. More important, psychostimulants significantly enhanced a measure of attention only when reinforcers were delayed, which may be reflective of the psychopharmacological mechanisms involved with clinical treatment of ADHD symptoms.
五选择连续反应时（5-CSRT）程序被认为是临床前研究中评估注意力心理药理学的一种转化工具。由于对延迟强化的更高敏感性可能会促进注意力缺陷多动障碍（ADHD）症状的发展，因此确定了强化延迟和精神兴奋剂对5-CSRT程序下行为表现的影响。雄性大鼠在具有不同强化延迟条件（0、2、4、8、16秒）的5-CSRT程序下接受训练，并在0秒和16秒延迟时评估右旋苯丙胺、哌甲酯和吗啡（作为阴性对照）的作用。在无药物条件下，随着延迟增加，反应潜伏期和无反应试验次数（遗漏）增加，而发出反应时的正确试验百分比降低。在0秒延迟条件下，精神兴奋剂仅使正确百分比有适度增加；然而，在16秒延迟时发现有更显著的提高。未观察到两种精神兴奋剂在任何一种延迟条件下对遗漏和反应潜伏期有一致的影响。吗啡在两种延迟条件下均增加了遗漏和反应潜伏期，并降低了正确百分比（16秒延迟）。一般来说，在任何条件下，试验间隔期间的反应均未受到系统性影响。当前结果表明，5-CSRT程序中的注意力测量对强化物递送延迟的变化敏感。更重要的是，仅当强化物延迟时，精神兴奋剂才显著增强了注意力测量，这可能反映了与ADHD症状临床治疗相关的心理药理学机制。
