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作为大鼠行为依赖性指标的听觉惊吓反应。

The acoustic startle response as a measure of behavioral dependence in rats.

作者信息

Mansbach R S, Gold L H, Harris L S

机构信息

Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0613.

出版信息

Psychopharmacology (Berl). 1992;108(1-2):40-6. doi: 10.1007/BF02245283.

Abstract

A series of experiments was conducted to assess the sensitivity of the acoustic startle response to chronic morphine administration and naloxone-precipitated withdrawal. Rats were implanted with two subcutaneous pellets containing either 75 mg each of morphine or containing only placebo. In experiment 1, withdrawal induced by 0.05-0.2 mg/kg naloxone dose-dependently decreased the magnitude of the startle response. Physical dependence was confirmed by a naloxone-induced acute weight loss seen in morphine-implanted rats, but naloxone had no effect on startle or body weight in non-dependent animals. In experiment 2, a modified procedure with fewer trials per session and fewer test days was employed. Naloxone (0.2 mg/kg) given 4-5 days after implantation induced large startle-response decreases in morphine-dependent rats while having no effect in placebo-implanted rats. Post-naloxone saline tests revealed no significant differences in startle between morphine and placebo groups. Startle scores were significantly higher in morphine-implanted rats than in placebo rats during a saline test given 3 days following pellet implantation. In a separate group of animals, however, acute IP injections of morphine from 0.3-10 mg/kg had no significant effect on startle amplitude. The effect of repeated pairings of withdrawal with the startle environment was assessed in experiment 3. Morphine-dependent rats startled significantly less if naloxone injections were given before the startle session than if they were administered 4 h later. Conditioned withdrawal effects, expressed during a final test session when all rats received saline, were observed for the body-weight measure but not for the startle response.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

进行了一系列实验,以评估慢性吗啡给药和纳洛酮诱发戒断对听觉惊吓反应的敏感性。给大鼠皮下植入两颗药丸,其中一颗含75毫克吗啡,另一颗仅含安慰剂。在实验1中,0.05 - 0.2毫克/千克剂量的纳洛酮诱发的戒断反应使惊吓反应的幅度呈剂量依赖性降低。吗啡植入大鼠中出现的纳洛酮诱发的急性体重减轻证实了身体依赖性,但纳洛酮对非依赖性动物的惊吓反应或体重没有影响。在实验2中,采用了一种每次试验次数和测试天数较少的改良程序。植入后4 - 5天给予纳洛酮(0.2毫克/千克),可使吗啡依赖性大鼠的惊吓反应大幅降低,而对植入安慰剂的大鼠没有影响。纳洛酮给药后的生理盐水测试显示,吗啡组和安慰剂组的惊吓反应没有显著差异。在植入药丸3天后进行的生理盐水测试中,吗啡植入大鼠的惊吓评分显著高于安慰剂大鼠。然而,在另一组动物中,0.3 - 10毫克/千克剂量的吗啡腹腔注射对惊吓幅度没有显著影响。在实验3中评估了戒断与惊吓环境重复配对的效果。如果在惊吓试验前给予纳洛酮注射,吗啡依赖性大鼠的惊吓反应明显小于在惊吓试验4小时后给予纳洛酮注射的情况。在最后一次测试中,当所有大鼠都接受生理盐水时,观察到体重测量出现了条件性戒断效应,但惊吓反应没有出现。(摘要截断于250字)

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