Yoshimura H, Ogawa N
Department of Pharmacology, Ehime University School of Medicine, Japan.
Eur J Pharmacol. 1991 Jul 23;200(1):147-53. doi: 10.1016/0014-2999(91)90677-i.
The present study investigated whether there is any difference between the effects of benzodiazepine and non-benzodiazepine anxiolytics on maternal aggression in lactating mice, using an ethological technique. We used SM-3997, a 5-HT1A receptor ligand, as a non-benzodiazepine anxiolytic. Behavior towards an intruder male mouse was assessed on postpartum days 5 and 7 in female mice that had been housed alone since the end of the 4-day mating period. Acute oral administration of diazepam had a biphasic effect on the frequency of bites: 1 mg/kg diazepam significantly increased bite frequency, while 2.5 mg/kg diazepam significantly decreased it. However, 2.5 mg/kg diazepam also caused a significant decrease in locomotor activity. In contrast, SM-3997 (1, 2.5 and 5 mg/kg p.o.) significantly decreased the frequency of bites in a dose-dependent manner without causing motor dysfunction. Chronic treatment with 5 mg/kg SM-3997 significantly decreased the frequency of bites when compared with vehicle, whereas diazepam was ineffective at the doses used (0.5 and 1 mg/kg p.o.). The findings suggest that the proaggressive effect is specific to benzodiazepines, and that 5-HT1A receptors may be involved in the suppression of maternal aggression in mice.
本研究采用行为学技术，调查了苯二氮䓬类和非苯二氮䓬类抗焦虑药对哺乳期小鼠母性攻击行为影响的差异。我们使用5-HT1A受体配体SM-3997作为非苯二氮䓬类抗焦虑药。在自4天交配期结束后一直单独饲养的雌性小鼠产后第5天和第7天，评估其对入侵雄性小鼠的行为。急性口服地西泮对咬的频率有双相作用：1mg/kg地西泮显著增加咬的频率，而2.5mg/kg地西泮则显著降低咬的频率。然而，2.5mg/kg地西泮也导致运动活性显著降低。相比之下，SM-3997（1、2.5和5mg/kg口服）以剂量依赖性方式显著降低咬的频率，且不会引起运动功能障碍。与赋形剂相比，5mg/kg SM-3997慢性治疗显著降低咬的频率，而地西泮在所使用的剂量（0.5和1mg/kg口服）下无效。这些发现表明，促攻击作用是苯二氮䓬类所特有的，并且5-HT1A受体可能参与抑制小鼠的母性攻击行为。
