Tsuji M, Takeda H, Matsumiya T
Department of Pharmacology and Intractable Disease Research Center, Tokyo Medical University, Japan.
Psychopharmacology (Berl). 2000 Oct;152(2):157-66. doi: 10.1007/s002130000514.
The effects of 5-HT(1A) receptor agonists on the emotional behavior of naive or stressed mice were examined and compared with those of benzodiazepine anxiolytics.
Changes in the emotional state of mice were evaluated in terms of changes in exploratory activity, i.e. total locomotor activity, numbers and duration of rearing and head-dipping and latency to the first head-dipping, using an automatic holeboard apparatus.
The 5-HT(1A) receptor full agonists flesinoxan (0.03-1 mg/kg, IP) and 8-OH-DPAT (0.03-1 mg/kg, IP), and the partial agonist buspirone (0.3-10 mg/kg, IP) dose-dependently decreased all of the exploratory behaviors. Significant decreases in both the number and duration of head-dips, and an increase in the latency to head-dipping were observed at 30 min after exposure to acute restraint stress (60 min). These emotional changes were scarcely improved by post-stress treatment with 5-HT(1A) receptor agonists, at doses that alone did not produce a significant behavioral effect. In contrast, pretreatment with flesinoxan (0.1-1 mg/kg, IP) or 8-OH-DPAT (0.1-1 mg/kg, IP) 24 h prior to exposure to stress dose-dependently suppressed the decrease in various exploratory behaviors that was observed immediately after the exposure to acute restraint stress. Moreover, pretreatment with buspirone (1-10 mg/kg, IP) 24 h prior to exposure to stress also significantly suppressed the decrease in rearing behavior and the increase in head-dip latency. However, changes in the emotional response to stress stimuli were not observed in mice that had been pretreated with the benzodiazepine anxiolytics diazepam (0.1-1 mg/kg, IP) and chlordiazepoxide (2-8 mg/kg, IP).
The present study clearly demonstrates that the behavioral effects of 5-HT(1A) receptor agonists in both naive and stressed mice were quite different from those of benzodiazepine anxiolytics, as previously reported by us. Notably, 5-HT(1A) receptor agonists but not benzodiazepine anxiolytics protect against various emotional changes produced by stress stimuli, and the results suggest that activation of 5-HT(1A) receptors may facilitate some mechanism(s) involved in the recognition of and/or ability to cope with stressful situation.
研究5-羟色胺（5-HT）1A受体激动剂对未受应激及应激小鼠情绪行为的影响，并与苯二氮䓬类抗焦虑药进行比较。
使用自动打洞板装置，根据探索活动的变化来评估小鼠情绪状态的改变，即总运动活动、竖毛和探头的次数及持续时间，以及首次探头的潜伏期。
5-HT1A受体完全激动剂氟司必林（0.03 - 1毫克/千克，腹腔注射）和8-羟基二丙胺基四氢萘（8-OH-DPAT，0.03 - 1毫克/千克，腹腔注射），以及部分激动剂丁螺环酮（0.3 - 10毫克/千克，腹腔注射）均剂量依赖性地降低所有探索行为。在急性束缚应激（60分钟）暴露后30分钟，观察到探头次数和持续时间显著减少，探头潜伏期增加。应激后用5-HT1A受体激动剂治疗，在单独使用时未产生显著行为效应的剂量下，这些情绪变化几乎未得到改善。相比之下，在暴露于应激前24小时用氟司必林（0.1 - 1毫克/千克，腹腔注射）或8-OH-DPAT（0.1 - 1毫克/千克，腹腔注射）预处理，剂量依赖性地抑制了急性束缚应激暴露后立即观察到的各种探索行为减少。此外，在暴露于应激前24小时用丁螺环酮（1 - 10毫克/千克，腹腔注射）预处理也显著抑制了竖毛行为的减少和探头潜伏期的增加。然而，在用苯二氮䓬类抗焦虑药地西泮（0.1 - 1毫克/千克，腹腔注射）和氯氮䓬（2 - 8毫克/千克，腹腔注射）预处理的小鼠中，未观察到对应激刺激的情绪反应变化。
本研究清楚地表明，5-HT1A受体激动剂在未受应激及应激小鼠中的行为效应与苯二氮䓬类抗焦虑药截然不同，正如我们之前所报道。值得注意的是，5-HT1A受体激动剂而非苯二氮䓬类抗焦虑药可预防应激刺激产生的各种情绪变化，结果表明5-HT1A受体的激活可能促进参与识别和/或应对应激情况能力的某些机制。
