Krsiak M, Sulcova A, Donat P, Tomasikova Z, Dlohozkova N, Kosar E, Masek K
Prog Clin Biol Res. 1984;167:93-114.
Majority of adult male albino random-bred mice housed singly or in small groups show agonistic behavior on interaction with a strange male mouse: some of them are predominantly aggressive ('aggressive' mice) while others show defenses or escapes even though their partners are not aggressive ('timid' mice). The remaining males not exhibiting agonistic behavior ('sociable' mice) show more social investigation then aggressive or timid mice and more locomotion then timid mice. Active defensive-escape behavior ('timidity') and inhibition of social investigation and of locomotion is much stronger in an unfamiliar cage with a strange male than in a home cage or on interaction with a female. Effects of 50 drugs on behavior of aggressive and timid male mice on agonistic interactions with non-aggressive male mice in neutral cages were tested. Most of the drugs possessing anxiolytic activity in man reduced active escapes or defenses at doses lower than those inhibiting attacks or locomotion and increased social investigation while most drugs without anxiolytic activity did not show these effects. Some anxiolytic drugs reduced tail-rattling (an ambivalent activity presumably reflecting both attack and escape tendency) at doses lower than those reducing attacks and increased locomotion. Only some benzodiazepines (nitrazepam, oxazepam and diazepam) produced the whole spectrum of these effects indicating a reduced defensive-escape tendency. The present results suggest that a selective inhibition of defensive-escape tendency on agonistic interactions can be a good predictor of anxiolytic activity of drugs. Profiles of effects of seven benzodiazepines in the present model of agonistic interaction to some extent differed: triazolam, clonazepam and flunitrazepam were more sedating (reduced timidity only at doses inhibiting locomotion) while nitrazepam, oxazepam, diazepam and chlordiazepoxide were less sedating (reduced timidity at non-sedative doses, stimulated social investigation and locomotion). Only drugs stimulating GABA-receptor complex (benzodiazepines, barbiturates and GABAergic drugs) inhibited active escapes and defenses at doses lower than those reducing attacks. This suggests that the GABA-receptor complex is involved in regulation of defensive-escape tendency in intraspecies conflict.
其中一些主要具有攻击性（“攻击性”小鼠），而另一些即使其伙伴没有攻击性也会表现出防御或逃避行为（“胆小”小鼠）。其余未表现出攻击行为的雄性（“社交性”小鼠）比攻击性或胆小的小鼠表现出更多的社交探索行为，比胆小的小鼠表现出更多的活动。在陌生笼子里与陌生雄性在一起时，主动防御 - 逃避行为（“胆小”）以及对社交探索和活动的抑制比在熟悉的笼子里或与雌性互动时要强得多。测试了50种药物对攻击性和胆小雄性小鼠在中性笼子里与非攻击性雄性小鼠进行攻击互动时行为的影响。大多数在人体中具有抗焦虑活性的药物在低于抑制攻击或活动的剂量时会减少主动逃避或防御行为，并增加社交探索行为，而大多数没有抗焦虑活性的药物则没有这些效果。一些抗焦虑药物在低于减少攻击行为的剂量时会减少尾巴颤动（一种可能反映攻击和逃避倾向的矛盾行为）并增加活动。只有一些苯二氮䓬类药物（硝西泮、奥沙西泮和地西泮）产生了所有这些效果，表明防御 - 逃避倾向降低。目前的结果表明，在攻击互动中对防御 - 逃避倾向的选择性抑制可能是药物抗焦虑活性的良好预测指标。在目前的攻击互动模型中，七种苯二氮䓬类药物的作用谱在一定程度上有所不同：三唑仑、氯硝西泮和氟硝西泮更具镇静作用（仅在抑制活动的剂量下才降低胆小行为），而硝西泮、奥沙西泮、地西泮和氯氮䓬的镇静作用较小（在非镇静剂量下降低胆小行为，刺激社交探索和活动）。只有刺激GABA受体复合物的药物（苯二氮䓬类、巴比妥类和GABA能药物）在低于减少攻击行为的剂量时会抑制主动逃避和防御行为。这表明GABA受体复合物参与了种内冲突中防御 - 逃避倾向的调节。
