Pharmacology Group, School of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, Avon BA2 7AY, UK.
J Psychopharmacol. 1992 Jan;6(2):241-57. doi: 10.1177/026988119200600218.
Clinical studies indicate that the behavioural responses/reactions of depressed patients to environmental and social stimulation are modified during remission from depressive illness, and require continuous (at least 3 weeks) drug treatment. In order to determine whether antidepressant drugs modify the behavioural patterns of experimental animals in ways that may be related to their ability to modify human reactive behaviour, we have examined the effects of acute and chronic treatment with clomipramine, fluoxetine, iprindole, mianserin and phenelzine (antidepressants with markedly different acute pharmacology) on the behaviour exhibited by rats during social interaction (SI). Acute treatment of short-term isolated resident rats with non-sedative doses of each antidepressant drug selectively and dose-relatedly reduced aggressive behaviour exhibited during SI. Conversely, haloperidol (antipsychotic) or diazepam (anxiolytic) only reduced aggressive behaviour at sedative doses. In comparison, following chronic treatment, all antidepressants examined, but not haloperidol or diazepam, increased aggressive behaviour exhibited by resident rats during SI which returned to the pre-treatment level by 7 or (after phenelzine) 14 days after the cessation of treatment. It is concluded that the antidepressants examined induce selective, diametrically opposite effects on rodent aggressive behaviour following acute and chronic treatment which is indicative of antidepressant efficacy. Furthermore, it is argued that the increased aggressive behaviour following chronic antidepressant drug treatment may indicate a disinhibition of social behaviour in the rat that mirrors the externalization of emotions associated with the remission of depressive illness.
临床研究表明,抑郁患者对环境和社会刺激的行为反应在抑郁缓解期间会发生改变,需要持续(至少 3 周)药物治疗。为了确定抗抑郁药是否以可能与其改变人类反应行为的能力相关的方式改变实验动物的行为模式,我们研究了氯米帕明、氟西汀、异丙吲哚、米氮平和苯乙肼(具有明显不同急性药理学的抗抑郁药)对社交互动(SI)期间大鼠表现出的行为的影响。急性短期隔离的常驻大鼠用每种抗抑郁药的非镇静剂量治疗,选择性地、剂量相关地减少了 SI 期间表现出的攻击行为。相反,氟哌啶醇(抗精神病药)或地西泮(抗焦虑药)仅在镇静剂量下才会减少攻击行为。相比之下,经过慢性治疗,所有研究的抗抑郁药都会增加常驻大鼠在 SI 期间表现出的攻击行为,但在治疗停止后 7 天(苯乙肼后)或 14 天恢复到治疗前水平。结论是,在所检查的抗抑郁药中,急性和慢性治疗后都会对啮齿动物的攻击行为产生选择性的、截然相反的影响,这表明了抗抑郁药的疗效。此外,有人认为,慢性抗抑郁药治疗后攻击性行为的增加可能表明大鼠的社会行为抑制解除,这反映了与抑郁缓解相关的情绪外化。