Söderpalm B, Engel J A
Department of Pharmacology, University of Göteborg, Sweden.
Life Sci. 1991;49(2):139-53. doi: 10.1016/0024-3205(91)90027-9.
The effects of drugs interacting with the GABAA/benzodiazepine chloride ionophore receptor complex (GABAA/BDZ-RC) on the anticonflict and biochemical effects observed after intracerebroventricular (i.c.v.) administration of 5,7-dihydroxytryptamine (5,7-DHT; 450 micrograms -14 days) were investigated in the rat using a modified Vogel's drinking conflict test. The GABAergic antagonistic drugs bicuculline, picrotoxin and Ro 15-4513 all counteracted the 5,7-DHT induced anxiolytic-like action in doses that did not alter the behavior per se, whereas flumazenil was ineffective in this respect. Also i.c.v. administration of 5-HT antagonized the 5,7-DHT induced anticonflict effect. Furthermore, 5,7-DHT-lesioned animals appeared more sensitive to the anticonflict effects of diazepam than sham-lesioned controls. The 5,7-DHT treatment produced marked depletions of 5-HT in the limbic system (80-90%) and hippocampus (90-95%), and an increase in the 5-HIAA/5-HT quotient in hippocampus. The effects on the levels of noradrenaline were comparatively small. The doses of bicuculline and picrotoxin antagonizing the 5,7-DHT induced anticonflict effect did not uniformly influence 5-HT levels or 5-HIAA/5-HT quotients. It is suggested that the anxiolytic-like effect observed in 5,7-DHT-lesioned rats in Vogel's drinking conflict test involves enhanced transmission at the GABAA/BDZ-RC.
利用改良的Vogel饮水冲突试验，在大鼠中研究了与GABAA/苯二氮䓬氯化物离子通道受体复合物（GABAA/BDZ-RC）相互作用的药物对脑室内（i.c.v.）注射5,7-二羟基色胺（5,7-DHT；450微克，持续14天）后观察到的抗冲突和生化效应的影响。GABA能拮抗药物荷包牡丹碱、印防己毒素和Ro 15-4513均能抵消5,7-DHT诱导的抗焦虑样作用，且所用剂量本身不会改变行为，而氟马西尼在这方面无效。脑室内注射5-羟色胺（5-HT）也能拮抗5,7-DHT诱导的抗冲突效应。此外，5,7-DHT损伤的动物似乎比假损伤对照组对 diazepam 的抗冲突效应更敏感。5,7-DHT处理使边缘系统（80-90%）和海马体（90-95%）中的5-HT显著减少，并使海马体中5-HIAA/5-HT比值增加。对去甲肾上腺素水平的影响相对较小。拮抗5,7-DHT诱导的抗冲突效应的荷包牡丹碱和印防己毒素剂量并未一致地影响5-HT水平或5-HIAA/5-HT比值。提示在Vogel饮水冲突试验中，5,7-DHT损伤大鼠中观察到的抗焦虑样效应涉及GABAA/BDZ-RC处的传递增强。
