Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA.
Eur J Pharmacol. 2013 Dec 5;721(1-3):201-7. doi: 10.1016/j.ejphar.2013.09.035. Epub 2013 Sep 25.
Antipsychotic drugs provide limited efficacy for cognitive impairment in schizophrenia. Recent studies have found that the neurotensin NTS1 receptor agonist and putative atypical antipsychotic drug PD149163 reverses deficits in sensory-gating and novel object recognition, suggesting that this compound may have the potential to improve cognitive functioning in schizophrenia. The present study sought to extend these investigations by evaluating the effects of PD149163 on sustained attention using a visual signal detection operant task in rats. PD149163, the atypical antipsychotic drug clozapine, and the dopamine D2/3 receptor antagonist raclopride all significantly decreased percent "hit" accuracy, while none of these compounds altered "correct rejections" (compared to vehicle control). Clozapine and raclopride significantly increased response latency, while high doses of PD149163 and raclopride significantly increased trial omissions. Nicotine, which was tested as a positive control, significantly improved overall performance in this task and did not affect response latency or trial omissions. The present findings suggest that neurotensin NTS1 receptor agonists, like antipsychotic drugs, may inhibit sustained attention in this task despite having different pharmacological mechanisms of action.
抗精神病药物对精神分裂症患者的认知障碍疗效有限。最近的研究发现，神经降压素 NTS1 受体激动剂和潜在的非典型抗精神病药 PD149163 可逆转感觉门控和新物体识别的缺陷，表明该化合物可能具有改善精神分裂症认知功能的潜力。本研究通过在大鼠视觉信号检测操作性任务中评估 PD149163 对维持注意力的影响，扩展了这些研究。PD149163、非典型抗精神病药氯氮平和多巴胺 D2/3 受体拮抗剂氯丙嗪均显著降低了“击中”准确率，而这些化合物均未改变“正确拒绝”（与载体对照相比）。氯氮平和氯丙嗪显著增加了反应潜伏期，而 PD149163 和氯丙嗪的高剂量显著增加了试验遗漏。尼古丁作为阳性对照进行了测试，显著改善了该任务的整体表现，且不影响反应潜伏期或试验遗漏。本研究结果表明，神经降压素 NTS1 受体激动剂，如抗精神病药，尽管具有不同的药理作用机制，也可能抑制该任务中的维持注意力。
