Stanhope K J, McLenachan A P, Dourish C T
Department of Neuropharmacology, Wyeth Research (UK) Limited, Berkshire, UK.
Psychopharmacology (Berl). 1995 Dec;122(3):268-80. doi: 10.1007/BF02246548.
The effects of the muscarinic antagonists scopolamine HBr and MeBr, the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), and the N-methyl-d-aspartate (NMDA) antagonists MK-801 and CGS-19755 on performance of rats in a delayed matching-to-position task were examined. Pretreatment with scopolamine HBr (0.05 and 0.1 mg/kg), resulted in a delay-dependent decrease in the percentage of correct responses and discriminability (log d), but had no effect on either the latency to complete trials, or the rate of trial completion during the fixed duration session. Scopolamine MeBr (0.1 mg/kg) did not impair percent correct or increase the response latency but did decrease the rate of trial completion. 8-OH-DPAT (up to 0.3 mg/kg), had no effect on percent correct, but did induce a small decrease in discriminability. The impairment in discriminability occurred only at a dose that substantially reduced the rate of trial completion. Both MK-801 (0.05 mg/kg) and CGS 19755 (10 mg/kg) induced a delay-independent impairment in percent correct, discriminability and a reduction in the rate of trial completion without affecting latency. A lower dose of CGS 19755 (5.0 mg/kg) induced a slight impairment in discriminability without significantly affecting the other measures. Taken together, these results demonstrate some dissociation between drug-induced cognitive and motor/motivational deficits in the DMTP test. However, the data question the specificity of putative cognitive impairments reported in many previous studies with the 5-HT1A agonist 8-OH-DPAT.
研究了毒蕈碱拮抗剂氢溴酸东莨菪碱和甲基溴东莨菪碱、5-羟色胺1A受体激动剂8-羟基-2-(二正丙基氨基)四氢萘(8-OH-DPAT)以及N-甲基-D-天冬氨酸(NMDA)拮抗剂MK-801和CGS-19755对大鼠在延迟位置匹配任务中表现的影响。用氢溴酸东莨菪碱(0.05和0.1毫克/千克)预处理后,正确反应百分比和辨别力(对数d)出现延迟依赖性下降,但对完成试验的潜伏期或固定时长试验期间的试验完成率均无影响。甲基溴东莨菪碱(0.1毫克/千克)不损害正确百分比或增加反应潜伏期,但确实降低了试验完成率。8-OH-DPAT(高达0.3毫克/千克)对正确百分比无影响,但确实导致辨别力略有下降。辨别力受损仅发生在显著降低试验完成率的剂量下。MK-801(0.05毫克/千克)和CGS 19755(10毫克/千克)均导致正确百分比、辨别力出现与延迟无关的损害,并降低试验完成率,且不影响潜伏期。较低剂量的CGS 19755(5.0毫克/千克)导致辨别力略有受损,而对其他指标无显著影响。综上所述,这些结果表明在延迟位置匹配试验中,药物诱导的认知缺陷与运动/动机缺陷之间存在一定的分离。然而,这些数据对许多先前使用5-羟色胺1A受体激动剂8-OH-DPAT的研究所报告的假定认知损害的特异性提出了质疑。