Paine Tracie A, Tomasiewicz Hilarie C, Zhang Kehong, Carlezon William A
Behavioral Genetics Laboratory, Department of Psychiatry, Harvard Medical School, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA.
Biol Psychiatry. 2007 Sep 15;62(6):687-93. doi: 10.1016/j.biopsych.2006.11.017. Epub 2007 Mar 7.
Attentional deficits accompany many psychiatric disorders, underscoring the need for rodent models of attention to screen novel therapeutic agents and characterize the biological basis of attention. The five-choice serial reaction time task (5CSRTT) is one such model. Here, we characterized the effects of four standard psychotropic agents on performance in the 5CSRTT.
Male Sprague-Dawley rats were trained in the 5CSRTT (5-sec inter-trial interval and .5-sec stimulus duration) until they reliably performed at > 60% accuracy and < 20% omissions. They were then treated systemically with the stimulant methylphenidate (MPH) (.063-2.0 mg/kg), the N-methyl-D-aspartate antagonist dizocilpine (MK-801) (.008-.25 mg/kg), the norepinephrine reuptake inhibitor desipramine (DMI) (.63-10 mg/kg), or the kappa-receptor agonist U69,593 (.25-2.0 mg/kg) 30 min before testing.
Methylphenidate (.5 mg/kg) increased accuracy. Dizocilpine impaired accuracy (.25 mg/kg), increased premature responses (.063-.25 mg/kg), and increased omissions (.25 mg/kg). Desipramine decreased premature responses (5.0 mg/kg) but increased omissions (10 mg/kg), correct response latencies (5.0-10.0 mg/kg), and reward latencies (5.0-10.0 mg/kg). The kappa-opioid agonist U69,593 (1.0-2.0 mg/kg) increased omissions and correct response latencies.
In Sprague-Dawley rats, psychotropic drugs with distinct pharmacological profiles produced distinguishable effects in the 5CSRTT. The effects of these classes of drugs under our testing conditions are qualitatively similar to their effects in humans.
注意力缺陷伴随许多精神疾病,这突出了需要啮齿动物注意力模型来筛选新型治疗药物并确定注意力的生物学基础。五选择连续反应时任务(5CSRTT)就是这样一种模型。在此,我们描述了四种标准精神药物对5CSRTT表现的影响。
雄性Sprague-Dawley大鼠在5CSRTT(5秒试验间隔和0.5秒刺激持续时间)中接受训练,直到它们以>60%的准确率和<20%的遗漏率稳定表现。然后在测试前30分钟,给它们全身注射兴奋剂哌甲酯(MPH)(0.063 - 2.0毫克/千克)、N-甲基-D-天冬氨酸拮抗剂地佐环平(MK-801)(0.008 - 0.25毫克/千克)、去甲肾上腺素再摄取抑制剂地昔帕明(DMI)(0.63 - 10毫克/千克)或κ-受体激动剂U69,593(0.25 - 2.0毫克/千克)。
哌甲酯(0.5毫克/千克)提高了准确率。地佐环平损害了准确率(0.25毫克/千克),增加了过早反应(0.063 - 0.25毫克/千克),并增加了遗漏率(0.25毫克/千克)。地昔帕明减少了过早反应(5.0毫克/千克),但增加了遗漏率(10毫克/千克)、正确反应潜伏期(5.0 - 10.0毫克/千克)和奖励潜伏期(5.0 - 10.0毫克/千克)。κ-阿片受体激动剂U69,593(1.0 - 2.0毫克/千克)增加了遗漏率和正确反应潜伏期。
在Sprague-Dawley大鼠中,具有不同药理学特征的精神药物在5CSRTT中产生了可区分的效应。在我们的测试条件下,这些类别的药物的效应在质量上与它们在人类中的效应相似。