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大鼠体内的γ-氨基丁酸能药物与冲突行为:与苯二氮䓬类药物作用缺乏相似性

GABAergic drugs and conflict behavior in the rat: lack of similarities with the actions of benzodiazepines.

作者信息

Agmo A, Pruneda R, Guzmán M, Gutiérrez M

机构信息

Department of Psychology, Unversidad Anáhuac, Mexico City, Mexico.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 1991 Sep;344(3):314-22. doi: 10.1007/BF00183006.

Abstract

Effects of drugs which enhance or reduce GABAergic neurotransmission upon conflict behavior were evaluated with a modified Vogel procedure which was shown to be insensitive to variations in motivation to drink and to the analgesic effects of morphine. In addition, the effects of these drugs on ambulatory activity and motor execution were quantified. For comparison, the benzodiazepines diazepam and chlordiazepoxide were used. Anticonflict actions of diazepam were obtained with a shock current of 0.25 mA but not with 0.05 or 0.5 mA, whereas the proconflict effect of FG7142 was obtained with 0.05 mA but not with higher currents. Diazepam and chlordiazepoxide had anxiolytic effect in a dose similar to that required to reduce ambulatory activity, but below that needed to affect motor execution. At doses high enough to impair motor execution, anticonflict effects were considerable. The GABA-A receptor agonist THIP and the GABA-B receptor agonist baclofen lacked effect on conflict behavior in moderate doses, which reduced ambulatory activity. In doses which produced motor deficiencies these drugs reduced licking both in the conflict test and when tested without shock administration. The effects of the GABA transaminase inhibitors gamma-acetylene GABA and sodium valproate were similar to those of the receptor agonists. The GABA reuptake inhibitor SKF 100330A produced anticonflict effect in a dose below that needed to reduce ambulatory activity, but lacked effect on conflict behavior in higher doses. The GABA antagonist picrotoxin, and the GABA synthesis inhibitors 4-deoxypyridoxine and isoniazide, reduced licking both in the absence and presence of shock, and affected motor functions in the same doses. Bicuculline, at the doses used, had no behavioral effects.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

采用改良的 Vogel 程序评估增强或降低 GABA 能神经传递的药物对冲突行为的影响,该程序已证明对饮水动机的变化以及吗啡的镇痛作用不敏感。此外,还对这些药物对自主活动和运动执行的影响进行了量化。为作比较,使用了苯二氮䓬类药物地西泮和氯氮䓬。地西泮的抗冲突作用在电击电流为 0.25 mA 时出现,而在 0.05 mA 或 0.5 mA 时未出现,而 FG7142 的促冲突作用在 0.05 mA 时出现,在更高电流时未出现。地西泮和氯氮䓬在与降低自主活动所需剂量相似的剂量下具有抗焦虑作用,但低于影响运动执行所需的剂量。在足以损害运动执行的高剂量下,抗冲突作用相当显著。GABA - A 受体激动剂 THIP 和 GABA - B 受体激动剂巴氯芬在中等剂量下对冲突行为无影响,这些剂量会降低自主活动。在产生运动缺陷的剂量下,这些药物在冲突试验中以及在无电击给药测试时均减少舔舐行为。GABA 转氨酶抑制剂γ - 乙炔基 GABA 和丙戊酸钠的作用与受体激动剂相似。GABA 再摄取抑制剂 SKF 100330A 在低于降低自主活动所需剂量时产生抗冲突作用,但在更高剂量下对冲突行为无影响。GABA 拮抗剂印防己毒素以及 GABA 合成抑制剂 4 - 脱氧吡哆醇和异烟肼在有无电击的情况下均减少舔舐行为,且在相同剂量下影响运动功能。在所使用的剂量下,荷包牡丹碱无行为学效应。(摘要截取自 250 字)

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