Anti-aggressive effects of agonists at 5-HT1B receptors in the dorsal raphe nucleus of mice
Anti-aggressive effects of agonists at 5-HT1B receptors in the dorsal raphe nucleus of mice
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DOI：
10.1007/s00213-007-0780-5
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发表时间：
2007-08-01
影响因子：
3.4
通讯作者：
Miczek, Klaus A.
中科院分区：
文献类型：
--
作者：
Bannai, Makoto;Fish, Eric W.;Miczek, Klaus A.
在啮齿动物中，5-羟色胺1B(5-HT1B)激动剂专门减少攻击行为，包括几种形式的升级攻击。一种形式的升级攻击是在小鼠身上看到的，这些小鼠通过在固定间隔(FI)时间表内加速反应来寻找攻击另一只小鼠的机会。目的研究两种5-HT1B受体激动剂对攻击动机和攻击行为的影响。材料与方法雄性小鼠作为“居住者”，以FI-10分钟为单位进行鼻戳反应，并有机会短暂攻击作为增强剂的“入侵者”。在第一个实验中，5-HT1B受体激动剂CP-94,253(0-10 mg/kg，ip)在FI10程序前30min给药。为证实CP-94、253的作用是通过5-HT1B受体实现的，在注射激动剂前给予5HT(1B/1D)受体拮抗剂GR 127935(10 mg/kg，ip)。实验二，在FI10刺激前10min，将5-HT1B激动剂CP-93,129(0~1.0 mg)微量注射到中缝背侧。CP-94,253和CP-93,129在低于影响操作员反应所需的剂量时，显著减少了对入侵者不断升级的攻击。最大剂量的CP-94,253(10 mg/kg)和CP-93,129(1.0 mU g)降低了FI10程序中的反应速度和加速模式；低剂量的效果较差。GR 127935可拮抗CP-94,253‘S对除反应率外的所有行为的作用。结论这些数据将5-HT1B激动剂的抗攻击作用扩展到一种奖励性攻击行为，并进一步提示这些作用与中缝背侧5-HT1B受体的作用有关。
Rationale In rodents, serotonin 1B (5-HT1B) agonists specifically reduce aggressive behaviors, including several forms of escalated aggression. One form of escalated aggression is seen in mice that seek the opportunity to attack another mouse by accelerating their responding during a fixed interval (FI) schedule. Responses preceding the opportunity to attack may reflect aggressive motivation.Objective This study investigated the effects of two 5-HT1B receptor agonists on the motivation to fight and the performance of heightened aggression.Materials & Methods Male mice were housed as "residents" and performed nose-poke responses on an FI 10-min schedule with the opportunity to briefly attack an "intruder" serving as the reinforcer. In the first experiment, the 5-HT1B receptor agonist, CP-94,253 (0-10 mg/kg, IP), was given 30 min before the FI 10 schedule. To confirm that CP-94,253 achieved its effects via 5-HT1B receptors, the 5HT(1B/1D) receptor antagonist, GR 127935 (10 mg/kg, IP) was administrated before the agonist injection. In the second experiment, the 5-HT1B agonist CP-93,129 (0-1.0 mu g) was microinjected into the dorsal raphe 10 min before the FI 10 schedule.Results The agonists had similar effects on all behaviors. CP-94,253 and CP-93,129 significantly reduced the escalated aggression towards the intruder at doses lower than those required to affect operant responding. The highest doses of CP-94,253 (10 mg/kg) and CP-93,129 (1.0 mu g) decreased the rate and accelerating pattern of responding during the FI 10 schedule; lower doses were less effective. GR 127935 antagonized CP-94,253's effects on all other behaviors, except response rate.Conclusions These data extend the anti-aggressive effects of 5-HT1B agonists to a type of escalated aggression that is rewarding and further suggest that these effects are associated with actions at 5-HT1B receptors in the dorsal raphe.