Strain differences in alcohol-induced neurochemical plasticity: A role for accumbens glutamate in alcohol intake
Strain differences in alcohol-induced neurochemical plasticity: A role for accumbens glutamate in alcohol intake
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DOI：
10.1111/j.1530-0277.2008.00620.x
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发表时间：
2008-04-01
影响因子：
3.2
通讯作者：
Szumlinski, Karen K.
中科院分区：
文献类型：
--
作者：
Kapasova, Zuzana;Szumlinski, Karen K.
背景资料：重复酒精给药改变了延髓核（NAC）的基础谷氨酸含量，并使酒精增加NAC细胞外谷氨酸水平的能力变得敏感。然而，酒精诱导的NAC谷氨酸变化与饮酒行为的相关性研究不足。为了研究NAC中饮酒的遗传变异与酒精诱导的神经适应之间的关系，在重复酒精处理的注射1和8中，在偏好酒精的C57 BL/6 J（B6）和避免酒精的DBA 2/J（D2）小鼠品系中进行体内微透析（8 x 2 g/kg，IP）。为了证实NAC谷氨酸在调节饮酒行为中的积极作用，谷氨酸再摄取抑制剂DL-苏型-β-苄氧基天冬氨酸（TBOA）（300 μ M）和第2组代谢型谷氨酸自身受体激动剂（2 R，4 R）-4-氨基吡咯烷-2，在4瓶选择试验中，在饮酒之前将4-二羧酸（APDC）（50 μ M）注入B6和D2小鼠的NAC中。虽然多巴胺，5-羟色胺或γ-氨基丁酸（GABA）的NAC基础水平的菌株差异不明显，重复酒精治疗升高NAC基础谷氨酸含量仅在B6小鼠。应变差异的急性和致敏的神经化学反应2克/公斤的酒精观察所有的神经递质检查。虽然酒精诱导的NAC多巴胺和谷氨酸水平升高在B6小鼠中致敏，但在D2动物中未观察到致敏。此外，B6小鼠表现出敏感的血清素和GABA响应酒精重复治疗后，而既不耐受，也不敏化观察D2动物。NAC APDC内输注可使B6和D2小鼠的酒精摄入量减少约50%。与此相反，TBOA输注酒精摄入量选择性升高B6 mice.Conclusions：这些数据表明NAC谷氨酸在调节小鼠酒精消耗量中的积极作用，并支持这一假设，即高酒精摄入量的易感性涉及遗传因素，促进酒精诱导的谷氨酸释放内NAC的适应。
Background: Repeated alcohol administration alters nucleus accumbens (NAC) basal glutamate content and sensitizes the capacity of alcohol to increase NAC extracellular glutamate levels. However, the relevance of alcohol-induced changes in NAC glutamate for alcohol drinking behavior is under-investigated.Methods: To examine the relationship between genetic variance in alcohol consumption and alcohol-induced neuroadaptations within the NAC, in vivo microdialysis was conducted in the alcohol-preferring C57BL/6J (B6) and alcohol-avoiding DBA2/J (D2) mouse strains on injections 1 and 8 of repeated alcohol treatment (8 x 2 g/kg, IP). To confirm an active role for NAC glutamate in regulating alcohol drinking behavior, the glutamate reuptake inhibitor DL-threo-beta-benzyloxyaspartic acid (TBOA) (300 mu M) and the Group 2 metabotropic glutamate autoreceptor agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC) (50 mu M) were infused into the NAC of B6 and D2 mice prior to alcohol consumption in a 4 bottle-choice test.Results: While strain differences were not apparent for NAC basal levels of dopamine, serotonin or gamma-amino butyric acid (GABA), repeated alcohol treatment elevated NAC basal glutamate content only in B6 mice. Strain differences in both the acute and the sensitized neurochemical responses to 2 g/kg alcohol were observed for all neurotransmitters examined. While the alcohol-induced rise in NAC dopamine and glutamate levels sensitized in B6 mice, a sensitization was not observed in D2 animals. Moreover, B6 mice exhibited a sensitized serotonin and GABA response to alcohol followed repeated treatment, whereas neither tolerance nor sensitization was observed in D2 animals. An intra-NAC APDC infusion reduced alcohol intake in both B6 and D2 mice by approximately 50%. In contrast, TBOA infusion elevated alcohol intake selectively in B6 mice.Conclusions: These data indicate an active role for NAC glutamate in regulating alcohol consumption in mice and support the hypothesis that predisposition to high alcohol intake involves genetic factors that facilitate alcohol-induced adaptations in glutamate release within the NAC.