Molewijk H E, van der Poel A M, Olivier B
Department of CNS Pharmacology, Solvay Duphar B.V., Weesp, The Netherlands.
Psychopharmacology (Berl). 1995 Sep;121(1):81-90. doi: 10.1007/BF02245594.
The effect of various psychotropic drugs on the ambivalent behaviour "stretched approach posture" (SAP) in the rat was assessed. SAP was elicited after a mild startle reaction due to physical contact with an electrified prod at one end of a straight runway. Using ethological observation methods, SAP as well as intention movements, prod contact, crossings, rearing, exploration, grooming and immobility were recorded. The benzodiazepine receptor agonists chlordiazepoxide, diazepam and alprazolam, the 5-HT1A receptor agonists flesinoxan and ipsapirone and the 5-HT uptake inhibitor clomipramine selectively (no effect on crossings) reduced SAP. Except for alprazolam, these drugs also reduced intention movements. In addition, chlordiazepoxide and diazepam enhanced prod contact. Reductions of SAP and intentions with concomitant reductions of crossings (nonspecific antiambivalent effects) were established for the alpha 2-adrenoceptor agonist clonidine and the MAO inhibitor clorgyline. The 5-HT uptake inhibitor fluvoxamine suppressed intention movements, but not SAP. The mixed 5-HT/NA uptake inhibitor imipramine did not significantly affect SAP or intentions, but reduced crossings. The 5-HT2C/1B receptor agonist m-CPP, the inverse BZD receptor agonists FG 7142 and DMCM, and the alpha 2-adrenoceptor antagonist yohimbine, to all of which putative anxiogenic effects have been ascribed, had no effect on SAP directed towards the prod. m-CPP, however, produced an increase in the stretched posture directed away from the prod (SAwayP). FG 7142 reduced intentions while strongly enhancing immobility (freezing). SAwayP and/or freezing may possibly reflect anxiogenic properties of drugs. The putative anxiogenic drug pentylenetetrazol false positively reduced SAP while increasing exploration. The dopamine-D2 receptor antagonist haloperidol and the catecholamine releaser dl-amphetamine had no effect on ambivalent behaviour. The muscarine receptor antagonist scopolamine reduced SAP and intentions while stimulating crossings. Finally, the 5-HT2C receptor antagonist ritanserine, the CCKA receptor antagonist devazepide, the CCKB receptor antagonist L-365.260 and the strychnine-insensitive glycine site antagonist 7-Cl-kynurenic acid were without effect on the behaviours in this paradigm using single doses. In conclusion, SAP and intention movements were reduced selectively by anxiolytic agents from different classes, including benzodiazepine receptor agonists, 5-HT1A receptor agonists and a 5-HT uptake inhibitor, whereas an alpha 2-adrenoceptor agonist and a MAO inhibitor reduced SAP non-selectively. SAP in relation to other behaviours may therefore serve as a valuable paradigm to characterize anxiolytic drugs.
评估了各种精神药物对大鼠矛盾行为“伸展接近姿势”（SAP）的影响。在大鼠与直跑道一端的带电探针发生身体接触而产生轻度惊吓反应后，引发SAP。采用行为学观察方法，记录了SAP以及意向动作、探针接触、穿越、竖毛、探索、梳理和静止不动等行为。苯二氮䓬受体激动剂氯氮卓、地西泮和阿普唑仑，5-HT1A受体激动剂氟司必林和伊沙匹隆，以及5-HT摄取抑制剂氯米帕明选择性地（对穿越无影响）减少了SAP。除阿普唑仑外，这些药物还减少了意向动作。此外，氯氮卓和地西泮增强了探针接触。α2-肾上腺素能受体激动剂可乐定和单胺氧化酶抑制剂氯吉兰减少了SAP和意向动作，同时也减少了穿越（非特异性抗矛盾作用）。5-HT摄取抑制剂氟伏沙明抑制了意向动作，但对SAP无影响。5-HT/NA混合摄取抑制剂丙咪嗪对SAP或意向动作无显著影响，但减少了穿越。5-HT2C/1B受体激动剂m-CPP、反向苯二氮䓬受体激动剂FG 7142和DMCM，以及α2-肾上腺素能受体拮抗剂育亨宾，所有这些药物都被认为具有潜在的致焦虑作用，但对指向探针的SAP均无影响。然而，m-CPP使远离探针的伸展姿势（SAwayP）增加。FG 7142减少了意向动作，同时强烈增强了静止不动（僵住）。SAwayP和/或僵住可能反映了药物的致焦虑特性。公认的致焦虑药物戊四氮错误地减少了SAP，同时增加了探索行为。多巴胺-D2受体拮抗剂氟哌啶醇和儿茶酚胺释放剂dl-苯丙胺对矛盾行为无影响。毒蕈碱受体拮抗剂东莨菪碱减少了SAP和意向动作，同时刺激了穿越行为。最后，5-HT2C受体拮抗剂利坦色林、CCKA受体拮抗剂地伐西匹、CCKB受体拮抗剂L-365.260和对士的宁不敏感的甘氨酸位点拮抗剂7-氯犬尿氨酸在单剂量使用时对该范式中的行为无影响。总之，不同类别的抗焦虑药物，包括苯二氮䓬受体激动剂（BZRAs）、5-HT1A受体激动剂和5-HT摄取抑制剂，选择性地减少了SAP和意向动作，而α2-肾上腺素能受体激动剂和单胺氧化酶抑制剂非选择性地减少了SAP。因此，与其他行为相关的SAP可能是一种有价值的范式，用于表征抗焦虑药物。
