Alcohol, allopregnanolone and aggression in mice
Alcohol, allopregnanolone and aggression in mice
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DOI：
10.1007/s002130000587
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发表时间：
2001-02-01
影响因子：
3.4
通讯作者：
Miczek, KA
中科院分区：
文献类型：
--
作者：
Fish, EW;Faccidomo, S;Miczek, KA
理由：在低剂量酒精的影响下，某些动物个体的攻击行为会大大增加。酒精的神经化学作用之一可能与酒精增强的攻击性（AHA）有关，这是它对GABA（A）受体复合物的正调节。目的：本研究的目的是调查酒精是否与GABA（A）受体复合物的内源性调节剂，神经甾体别孕烯醇酮，在刺激/提高攻击行为。方法ANN结果：第一个实验的目的是检验GABA（A）受体复合物的神经类固醇调节剂会增加攻击性的假设，并将这些效果与酒精进行比较。雄性CFW小鼠注射别孕烯醇酮、阿法沙龙（3-30 mg/kg，IP）或酒精（1.0 g/kg，PO）15 min，然后与入侵者对抗5 min。适量的酒精和神经类固醇增加了攻击性。高于基线50%;仅在最高剂量下观察到运动受损。第二个实验通过给予别孕烯醇酮（1-10 mg/kg）同时口服注射酒精（0.6或1.0 g/kg）或水来比较AHA和ANA（即酒精非增强攻击性）小鼠。当给予水和0.6 g/kg剂量的酒精时，allopregnanolone增加了AHA和ANA小鼠的攻击性。在ANA小鼠中给予1.0 g/kg剂量的酒精可防止异孕烯醇酮升高的攻击性。在AHA小鼠中，在1.0 g/kg酒精中加入别孕烯醇酮剂量依赖性地降低了酒精增强的攻击性，这表明酒精对攻击性的抑制作用增强。结论：神经活性类固醇allopregnanolone似乎在酒精增强的攻击性中发挥重要作用。此外，酒精的攻击性增强作用的上移和别孕烯醇酮在最大有效酒精剂量下的下移指向GABA（A）受体复合物的两种正调节剂的共同机制。
Rationale: Aggressive behavior of certain individual animals can be greatly increased when under the influence of low doses of alcohol. One of alcohol's neurochemical actions that may be relevant to alcohol-heightened aggression (AHA) is its positive modulation of the GABA(A) receptor complex. Objective: The objective of this study was to investigate whether alcohol interacts with an endogenous modulator of the GABA(A) receptor complex, the neurosteroid allopregnanolone, in stimulating/heightening aggressive behavior. Methods ann results: The first experiment was designed to test the hypothesis that neurosteroid modulators of the GABA(A) receptor complex will increase aggression and to compare these effects with alcohol. Male CFW mice were injected with allopregnanolone, alphaxalone (3-30 mg/kg, IP), or alcohol (1.0 g/kg, PO) 15 min prior to a 5-min confrontation with an intruder. Moderate doses of alcohol and the neurosteroids increased aggression by ca. 50% above baseline; impaired locomotion was seen only at the highest doses. A second experiment compared AHA and ANA (i.e. alcohol-non-heightened aggression) mice by giving allopregnanolone (1-10 mg/kg) with a simultaneous oral injection of alcohol (0.6 or 1.0 g/kg) or water. When administered with water and the 0.6 g/kg dose of alcohol, allopregnanolone increased the aggression of AHA and ANA mice. Administration of the 1.0 g/kg dose of alcohol in ANA mice prevented allopregnanolone-heightened aggression. In AHA mice, addition of allopregnanolone to 1.0 g/kg alcohol dose-dependently reduced alcohol-heightened aggression, suggesting potentiation of alcohol's suppressive effects on aggression. Conclusions: The neuroactive steroid allopregnanolone appears to play an important role in alcohol-heightened aggression. Moreover, the upward shift of the aggression-heightening effects of alcohol and the downward shift at the maximally effective alcohol dose by allopregnanolone point to a shared mechanism for both positive modulators of the GABA(A) receptor complex.