Nikiforuk Agnieszka, Popik Piotr
Department of Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland.
Department of Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland.
Eur Neuropsychopharmacol. 2014 Aug;24(8):1381-93. doi: 10.1016/j.euroneuro.2014.04.007. Epub 2014 May 4.
Ketamine, the non-competitive antagonist of the N-methyl-d-aspartate receptors, is used in clinical and preclinical studies to produce schizophrenia-like cognitive impairments. However, the impact of ketamine on attentional functions remains poorly characterised. In the present study, we further examine the effects of ketamine on attentional processes assessed in the five-choice serial reaction time task (5-CSRTT) in rats. The applied schedules of ketamine administration have been previously demonstrated to evoke frontal-dependent set-shifting impairments. Rats were trained to reach a stable baseline performance. Afterwards, animals received a single injection of ketamine (0, 3 and 10 mg/kg, IP) 45 min before the 5-CSRTT session (experiment 1). In experiment 2, ketamine (0 and 30 mg/kg, IP) was administered after the daily test session for 10 consecutive days. The rats' performance was assessed at 22 h following ketamine administration and for 4 days after the last dose. Acute and repeated administration of ketamine disrupted rats performance on the 5-CSRTT. Reduced speed of responding and an increased number of omissions were noted in the absence of reduced food motivation. The within-session pattern of responding differed between rats treated acutely and repeatedly with ketamine. Specifically, repeated drug administration evoked an increase in omissions toward the end of the session, and this effect was not secondary to the reduced motivation. Ketamine affected performance during the withdrawal period only when testing with variable inter-trial intervals. The repeated administration of ketamine can impair rats' ability to sustain attention over the course of session, suggesting some utility for modelling attentional disturbances.
氯胺酮是 N-甲基-D-天冬氨酸受体的非竞争性拮抗剂，在临床和临床前研究中用于产生类似精神分裂症的认知障碍。然而，氯胺酮对注意力功能的影响仍未得到充分表征。在本研究中，我们进一步研究了氯胺酮对大鼠在五选择连续反应时任务（5-CSRTT）中评估的注意力过程的影响。先前已证明应用的氯胺酮给药方案会引起额叶依赖性的定势转换障碍。大鼠经过训练以达到稳定的基线表现。之后，动物在 5-CSRTT 实验前 45 分钟接受单次氯胺酮注射（0、3 和 10 mg/kg，腹腔注射）（实验 1）。在实验 2 中，氯胺酮（0 和 30 mg/kg，腹腔注射）在每日测试实验后连续 10 天给药。在氯胺酮给药后 22 小时以及最后一剂后 4 天评估大鼠的表现。氯胺酮的急性和重复给药扰乱了大鼠在 5-CSRTT 上的表现。在食物动机未降低的情况下，观察到反应速度降低和遗漏次数增加。氯胺酮急性和重复给药的大鼠在实验过程中的反应模式有所不同。具体而言，重复给药会导致实验接近尾声时遗漏次数增加，并且这种影响并非继发于动机降低。仅在采用可变的试验间隔进行测试时，氯胺酮在撤药期会影响表现。氯胺酮的重复给药会损害大鼠在实验过程中维持注意力的能力，这表明其在模拟注意力障碍方面具有一定作用。
