NMDA receptor antagonism: escalation of aggressive behavior in alcohol-drinking mice.
NMDA receptor antagonism: escalation of aggressive behavior in alcohol-drinking mice.
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DOI：
10.1007/s00213-012-2734-9
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发表时间：
2012-11
影响因子：
3.4
通讯作者：
Miczek, Klaus A.
中科院分区：
文献类型：
--
作者：
Newman, Emily L.;Chu, Adam;Bahamon, Brittany;Takahashi, Aki;DeBold, Joseph F.;Miczek, Klaus A.
美金刚是一种潜在的治疗酒精患者的方法，但很少有研究探讨美金刚和乙醇同时治疗对攻击行为的影响。我们评估了乙醇消耗和谷氨酸能药物治疗后的攻击行为，以表征这些化合物之间的相互作用。利用啮齿动物的攻击模型来研究谷氨酸能化合物和乙醇之间的相互作用。一旦雄性CFW小鼠可靠地自我给药1 g/kg乙醇或水，它们在居民-入侵者对抗中的攻击性被评估。另一种方法是，根据社会教唆程序评估攻击性。然后在攻击对抗前给动物注射美金刚胺、氯胺酮、奈拉美辛、MTEP或LY379268。分析药理学手法对大鼠显著攻击行为和非攻击行为的影响。中等剂量的美金刚、奈拉美珊和MTEP与乙醇相互作用，增加攻击咬伤的频率，而氯胺酮则没有。最高剂量的mGluR2/3激动剂LY379268在水和乙醇自我给药后减少了攻击和非攻击行为。攻击咬伤随社会唆使而增加，随高剂量MTEP和LY379268的施用而减少。刚胺和MTEP均能降低刺激条件下的攻击咬伤频率，但不影响运动行为。美金刚和奈拉美珊与乙醇相互作用增强攻击性。这些化合物的结合特性允许“部分捕获”，从而使一些NMDARs在去极化之间不被阻断。我们认为，这一特征可能有助于这些化合物与乙醇之间不同的增强侵蚀作用。MTEP还与乙醇相互作用，可能通过抑制mGluR5对NMDARs的调节来增强攻击。
Memantine is a potential treatment for alcoholic patients, yet few studies investigate the effect of concurrent treatment with memantine and ethanol on aggression. We evaluated aggressive behavior following ethanol consumption and treatment with glutamatergic drugs to characterize interactions between these compounds. To use rodent models of aggression to examine interactions between glutamatergic compounds and ethanol. Once male CFW mice reliably self-administered 1 g/kg ethanol or water, they were assessed for aggression in resident-intruder confrontations. Alternatively, aggression was evaluated following a social-instigation procedure. Animals were then injected with memantine, ketamine, neramexane, MTEP or LY379268 before aggressive confrontations. Effects of the pharmacological manipulations on salient aggressive and non-aggressive behaviors were analyzed. Moderate doses of memantine, neramexane and MTEP interacted with ethanol to increase the frequency of attack bites while ketamine did not. The highest dose of LY379268, an mGluR2/3 agonist, reduced both aggressive and non-aggressive behaviors after water and ethanol self-administration. Attack bites increased with social instigation and decreased with administration of high doses of MTEP and LY379268. Memantine and MTEP both reduced attack bite frequency in the instigation condition without reducing locomotor behavior. Memantine and neramexane interacted with ethanol to heighten aggression. The binding characteristics of these compounds allow for ‘partial trapping’ by which some NMDARs are unblocked between depolarizations. We propose that this feature may contribute to the differential aggression-heightening interactions between these compounds and ethanol. MTEP also interacted with ethanol to escalate aggression, possibly through inhibition of mGluR5 modulation of NMDARs.
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影响因子：
5
作者：
Bienkowski, P;Krzascik, P;Danysz, W
通讯作者：
Danysz, W
影响因子：
3.4
作者：
Bannai, Makoto;Fish, Eric W.;Miczek, Klaus A.
通讯作者：
Miczek, Klaus A.
影响因子：
2.5
作者：
Blanpied, TA;Boeckman, FA;Johnson, JW
通讯作者：
Johnson, JW
影响因子：
5.3
作者：
Celada, P;Puig, MV;Artigas, F
通讯作者：
Artigas, F
影响因子：
2.9
作者：
Hassanain, M;Bhatt, S;Siegel, A
通讯作者：
Siegel, A