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苯环利定、(+)-SKF-10,047和MK-801对大鼠脑电图及行为的比较影响

Comparative electroencephalographic and behavioral effects of phencyclidine, (+)-SKF-10,047 and MK-801 in rats.

作者信息

Marquis K L, Paquette N C, Gussio R P, Moreton J E

机构信息

Department of Pharmacology and Toxicology, University of Maryland School of Pharmacy, Baltimore.

出版信息

J Pharmacol Exp Ther. 1989 Dec;251(3):1104-12.

PMID:2557412
Abstract

Female Sprague-Dawley rats prepared with chronic i.v. cannulas and/or cerebrocortical electrodes were administered sequentially increasing doses of phencyclidine (PCP, 0.1-6.4 mg/kg/injection), (+)-SKF-10,047 [(+)-N-allynormetazocine] (0.4-25.6 mg/kg/injection) or MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine maleate] (0.01-0.64 mg/kg/injection). Effects on overt behavior, cortical EEG power spectra, locomotor activity and rotarod performance were assessed. Quantitative EEG spectral parameters (peak, mean and edge frequency; total and relative power; time domain descriptors mobility and complexity) were analyzed from the global frequency range of 1 to 50 Hz. Increasing doses of each drug produced increases in EEG spectra power from 1 to 50 Hz which was associated with a slowing of the peak frequency. PCP and MK-801 produced decreases in the mean frequency, mobility and edge frequency whereas (+)-SKF-10,047 produced increases in these spectral parameters. Moreover, (+)-SKF-10,047 increased complexity whereas MK-801 decreased complexity and PCP did not change this parameter. Total spectral power from 20 to 50 Hz was increased by (+)-SKF-10,047 and PCP, but was not changed by MK-801. Each drug increased spontaneous locomotor activity. At the highest doses, PCP and MK-801 decreased activity whereas (+)-SKF-10,047 was lethal. Each drug disrupted rotarod performance. The rank order of potency for each effect was: MK-801 greater than PCP greater than (+)-SKF-10,047. The data indicate that subtle differences in the effects of these drugs can be detected using EEG power spectral analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

给制备了慢性静脉插管和/或脑皮质电极的雌性斯普拉格-道利大鼠依次给予递增剂量的苯环利定(PCP,0.1 - 6.4毫克/千克/注射)、(+)-SKF-10,047 [(+)-N-烯丙基去甲左啡诺](0.4 - 25.6毫克/千克/注射)或MK-801 [(+)-5-甲基-10,11-二氢-5H-二苯并[a,d]环庚烯-5,10-亚胺马来酸盐](0.01 - 0.64毫克/千克/注射)。评估对明显行为、皮质脑电图功率谱、运动活动和转棒试验表现的影响。从1至50赫兹的全频率范围分析定量脑电图频谱参数(峰值、平均和边缘频率;总功率和相对功率;时域描述符迁移率和复杂度)。每种药物剂量增加均使1至50赫兹的脑电图频谱功率增加,这与峰值频率减慢有关。PCP和MK-801使平均频率、迁移率和边缘频率降低,而(+)-SKF-10,047使这些频谱参数增加。此外,(+)-SKF-10,047增加了复杂度,而MK-801降低了复杂度,PCP未改变此参数。20至50赫兹的总频谱功率被(+)-SKF-10,047和PCP增加,但未被MK-801改变。每种药物均增加自发运动活动。在最高剂量时,PCP和MK-801降低活动,而(+)-SKF-10,047是致命的。每种药物均破坏转棒试验表现。每种效应的效价顺序为:MK-801大于PCP大于(+)-SKF-10,047。数据表明,使用脑电图功率谱分析可以检测到这些药物效应的细微差异。(摘要截短于250字)

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