Rodgers R J, Waters A J
Physiol Behav. 1984 Sep;33(3):401-9. doi: 10.1016/0031-9384(84)90161-6.
In view of recently reported low-dose behavioural activity of Ro 15-1788, the present study examined the effects of this benzodiazepine antagonist on social and agonistic behaviours in adult male albino mice. Using a resident-intruder paradigm, independent pharmacological manipulation of interactants and pharmaco-ethological analysis, our data demonstrate significant behavioural effects of Ro 15-1788 in benzodiazepine-naive animals. In residents, treatment with the antagonist (1.25, 2.5, 10 and 20 mg/kg, IP) resulted in dose-related increases in offensive threat behaviour and reduced olfactory investigation. However, 5 mg/kg exerted no detectable behavioural action in these animals. In intruders, behavioural effects were observed only with 1.25 mg/kg Ro 15-1788, and consisted of a profile suggestive of reduced defensiveness. In both experiments, the behaviour of untreated opponents confirmed the existence of drug-induced behavioural changes in their partners. It is argued that present data are not inconsistent with the existence of putative endogenous benzodiazepine-like ligands and that the differential effects of Ro 15-1788 in residents (singly-housed) and intruders (grouped) suggest one possible explanation for previous failures to detect low-dose behavioural activity with this compound.
鉴于最近报道的Ro 15-1788的低剂量行为活性,本研究考察了这种苯二氮䓬拮抗剂对成年雄性白化小鼠社交和攻击行为的影响。采用居住者-入侵者范式、对互动者进行独立的药理学操作以及药物行为学分析,我们的数据表明Ro 15-1788对未接触过苯二氮䓬的动物具有显著的行为影响。对于居住者,给予拮抗剂(1.25、2.5、10和20 mg/kg,腹腔注射)导致攻击性威胁行为呈剂量相关增加,嗅觉探究减少。然而,5 mg/kg在这些动物中未产生可检测到的行为作用。对于入侵者,仅在给予1.25 mg/kg Ro 15-1788时观察到行为影响,表现为防御性降低。在两个实验中,未处理的对手的行为证实了其伙伴中存在药物诱导的行为变化。有人认为,目前的数据与假定的内源性苯二氮䓬样配体的存在并不矛盾,并且Ro 15-1788在居住者(单独饲养)和入侵者(群居)中的不同作用为之前未能检测到该化合物的低剂量行为活性提供了一种可能的解释。