Söderpalm B, Hjorth S, Engel J A
Department of Pharmacology, University of Göteborg, Sweden.
Pharmacol Biochem Behav. 1989 Jan;32(1):259-65. doi: 10.1016/0091-3057(89)90242-6.
The effects of the pyrimidinyl-piperazines buspirone, gepirone, ipsapirone and their common metabolite 1-(2-pyrimidinyl)-piperazine (PmP) as well as of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and L-5-hydroxytryptophan (L-5-HTP) were investigated in Montgomery's conflict test--an animal anxiety model based on the animal's inborn urge to explore a new environment and its simultaneous fear of elevated, open spaces. Subcutaneous buspirone (32-128 nmol/kg), gepirone (32-128 nmol/kg), ipsapirone (32-512 nmol/kg) and 8-OH-DPAT (50-200 nmol/kg), as well as intraperitoneal L-5-HTP (56 mumol/kg) produced anxiolytic-like effects. However, at higher doses the magnitude of these effects decreased and overall the dose-response curves displayed inverted U-shapes. The highest doses (2048 nmol/kg) of buspirone and of gepirone even decreased responding below control levels, possibly in part due to concomitant sedation/motor impairment. After L-5-HTP (448 mumol/kg) and PmP (512 nmol/kg) anxiogenic-like effects were observed. The results indicate that anxiolytic- and anxiogenic-like effects of drugs affecting central serotonergic neurotransmission can be obtained in a sensitive rat anxiety model which neither involves consummatory behavior nor punishment. The anxiolytic-like effects of these compounds may be due to their 5-HT1A agonistic properties. Moreover, the present data may provide support for a possible reciprocal association of presynaptic 5-HT1A receptors vs. postsynaptic 5-HT1A as well as 5-HT2 receptors with regard to anxiety.
在蒙哥马利冲突试验（一种动物焦虑模型，基于动物探索新环境的天生冲动及其同时对高处、开阔空间的恐惧）中，研究了嘧啶基哌嗪类药物丁螺环酮、吉哌隆、伊沙匹隆及其共同代谢物1-(2-嘧啶基)-哌嗪（PmP）以及8-羟基-2-(二正丙基氨基)四氢萘（8-OH-DPAT）和L-5-羟色氨酸（L-5-HTP）的作用。皮下注射丁螺环酮（32 - 128 nmol/kg）、吉哌隆（32 - 128 nmol/kg）、伊沙匹隆（32 - 512 nmol/kg）和8-OH-DPAT（50 - 200 nmol/kg），以及腹腔注射L-5-HTP（56 μmol/kg）产生了抗焦虑样作用。然而，在较高剂量时，这些作用的程度降低，总体剂量反应曲线呈倒U形。丁螺环酮和吉哌隆的最高剂量（2048 nmol/kg）甚至使反应低于对照水平，这可能部分归因于伴随的镇静/运动功能损害。在给予L-5-HTP（448 μmol/kg）和PmP（512 nmol/kg）后，观察到了致焦虑样作用。结果表明，在一种既不涉及消费行为也不涉及惩罚的敏感大鼠焦虑模型中，可以获得影响中枢5-羟色胺能神经传递的药物的抗焦虑样和致焦虑样作用。这些化合物的抗焦虑样作用可能归因于它们的5-HT1A激动特性。此外，目前的数据可能为突触前5-HT1A受体与突触后5-HT1A以及5-HT2受体在焦虑方面可能的相互关联提供支持。
