Olivier B, Mos J, van Oorschot R, Hen R
CNS-Pharmacology, Solvay Duphar B.V., Weesp, The Netherlands.
Pharmacopsychiatry. 1995 Oct;28 Suppl 2:80-90. doi: 10.1055/s-2007-979624.
Various models of rodent agonistic behavior are described, which differentiate between offensive and defensive/flight models. Particular attention is given to one male and one female paradigm for offensive aggression, i.e. resident/intruder or territorial aggression (RI) and maternal aggression (MA). After an overview of the serotonin (5-HT) system in the CNS, a description is given of the ligands available. Subsequently, the effects of various drugs affecting serotonergic transmission in the RI- and MA-paradigms are described. The 5-HT1A receptor agonists busipirone, ipsapirone, and 8-OH-DPAT decreased aggression in RI and MA, but simultaneously led to a marked decrease in social interest and activity, indicative of a nonspecific antiaggressive profile. Nonselective 5-HT1 receptor agonists, such as RU24969, eltoprazine, and TFMPP reduced aggression quite specifically, did not decrease social interest or exploration, and sometimes even increased these behaviors. In RI and MA, the behavioral effects of these drugs were roughly similar. In contrast, MA was more sensitive to treatment with the 5-HT reuptake blocker fluvoxamine, which blocked RI aggression nonspecifically at the highest dose only. DOI, a 5-HT2A/2C# receptor agonist, decreased aggressive behavior and increased inactivity, without affecting social interest and exploration in RI as well as MA. This was, however, accompanied by "wet dog shaking" characteristic of 5-HT2 receptor stimulation. The nonspecific 5-HT receptor agonist (and 5-HT2 receptor antagonist) quipazine also induced "wet dog shaking" at doses which suppressed aggression, social interest, and exploration but increased inactive behaviors (sitting and lying). The discussion delineates a specific role for 5-HT1B receptor-subtype involvement in the modulation of aggression, with the restrictions we clearly face with regard to the lack of specific serotonergic agonists and antagonists for certain receptor subtypes. By and large, male and female rats react similarly to treatment with serotonergic drugs, and this fact underlines the consistent role of 5-HT in different forms of aggression.
本文描述了多种啮齿动物攻击行为模型，这些模型区分了进攻性和防御性/逃跑性模型。特别关注了一种用于进攻性攻击的一雄一雌范式，即领地/入侵者或领地攻击（RI）和母性攻击（MA）。在概述中枢神经系统中的血清素（5-HT）系统后，介绍了可用的配体。随后，描述了各种影响RI和MA范式中血清素能传递的药物的作用。5-HT1A受体激动剂丁螺环酮、伊沙匹隆和8-OH-DPAT可降低RI和MA中的攻击性，但同时导致社交兴趣和活动显著减少，表明其具有非特异性抗攻击特征。非选择性5-HT1受体激动剂，如RU24969、依托必利和TFMPP相当特异性地降低了攻击性，并未降低社交兴趣或探索行为，有时甚至增加了这些行为。在RI和MA中，这些药物的行为效应大致相似。相比之下，MA对5-HT再摄取阻滞剂氟伏沙明的治疗更敏感，氟伏沙明仅在最高剂量时非特异性地阻断RI攻击。DOI是一种5-HT2A/2C#受体激动剂，可降低攻击行为并增加不活动状态，而不影响RI和MA中的社交兴趣和探索行为。然而，这伴随着5-HT2受体刺激特有的 “湿狗摇晃”。非特异性5-HT受体激动剂（也是5-HT2受体拮抗剂）喹哌嗪在抑制攻击、社交兴趣和探索行为但增加不活动行为（坐着和躺着）的剂量下也会诱导 “湿狗摇晃”。讨论阐述了5-HT1B受体亚型在攻击调节中的特定作用，同时也指出了我们在缺乏某些受体亚型的特异性血清素能激动剂和拮抗剂方面所面临的明显限制。总体而言，雄性和雌性大鼠对血清素能药物治疗的反应相似，这一事实强调了5-HT在不同形式攻击中的一致作用。
