Fish Eric W, DeBold Joseph F, Miczek Klaus A
Department of Psychology, Tufts University, Medford, MA, USA.
Psychopharmacology (Berl). 2005 Oct;182(1):116-27. doi: 10.1007/s00213-005-0064-x. Epub 2005 Aug 13.
Individuals seek out the opportunity to fight, but the mechanisms behind this positively reinforcing effect of aggression have yet to be understood.
The aims of this study were to (1) describe behavioral and corticosterone elevations that occur in aggressive mice conditioned to respond for the opportunity to fight another mouse, (2) determine if corticosterone elevations are necessary for operant responding and escalated aggression, and (3) determine if corticosterone elevations alter the aggression-heightening effects of gamma-aminobutyric acid (GABA)(A) receptor positive modulators.
Aggressive male CFW mice were conditioned to respond under the control of a fixed-interval 10-min (FI10) schedule that reinforced their operant behavior by the presentation of an intruder mouse into their home cage. After the FI10, aggressive behavior was ca. 75% higher than the species-typical levels of fighting and plasma corticosterone was more than twice as high after briefly fighting and/or responding on the FI10 schedule. Inhibition of corticosterone synthesis by metyrapone (30-100 mg/kg) reduced both conditioned responding as well as the aggressive behavior after the FI. Although the benzodiazepine midazolam (0.3-3 mg/kg) heightened species-typical aggressive behavior, it did not increase the high level of aggression engendered by the FI schedule. However, midazolam (0.3 mg/kg) and the neurosteroid allopregnanolone (17 mg/kg) both heightened aggression when given after corticosterone synthesis inhibition by metyrapone (56 mg/kg).
These data suggest that corticosterone elevations are required for responding that is motivated by aggressive behavior and for escalated aggression that follows this responding. Corticosterone elevations also appear to inhibit the aggression heightening effect of GABA(A) receptor positive modulators.
个体主动寻求战斗机会，但其背后的积极强化作用机制仍不清楚。
本研究旨在（1）描述在条件性攻击小鼠中出现的行为和皮质酮升高情况，这些小鼠被训练为通过有机会与另一只小鼠战斗来做出反应；（2）确定皮质酮升高对于操作性反应和攻击性升级是否必要；（3）确定皮质酮升高是否会改变γ-氨基丁酸（GABA）（A）受体阳性调节剂的攻击增强作用。
将具有攻击性的雄性CFW小鼠训练为在固定间隔10分钟（FI10）的时间表控制下做出反应，通过将一只入侵小鼠放入其家笼来强化其操作性行为。在FI10之后，攻击性行为比该物种典型的战斗水平高约75%，并且在短暂战斗和/或按照FI10时间表做出反应后，血浆皮质酮水平高出两倍多。美替拉酮（30 - 100 mg/kg）抑制皮质酮合成可降低条件性反应以及FI之后的攻击性行为。虽然苯二氮䓬类药物咪达唑仑（0.3 - 3 mg/kg）可增强该物种典型的攻击性行为，但它并未增加FI时间表所引发的高水平攻击性行为。然而，在美替拉酮（56 mg/kg）抑制皮质酮合成后给予咪达唑仑（0.3 mg/kg）和神经甾体别孕烯醇酮（17 mg/kg），二者均增强了攻击性行为。
这些数据表明，皮质酮升高对于由攻击性行为驱动的反应以及该反应之后的攻击性升级是必需的。皮质酮升高似乎还会抑制GABA（A）受体阳性调节剂的攻击增强作用。
