Enhanced AMPA receptor activity increases operant alcohol self-administration and cue-induced reinstatement.
Enhanced AMPA receptor activity increases operant alcohol self-administration and cue-induced reinstatement.
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DOI：
10.1111/adb.12000
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发表时间：
2013-01
影响因子：
3.4
通讯作者：
Hodge CW
中科院分区：
文献类型：
--
作者：
Cannady R;Fisher KR;Durant B;Besheer J;Hodge CW
长期酒精暴露会产生神经适应性，从而导致酒精滥用障碍的发展。在动物模型中，慢性饮酒导致兴奋性神经传递增强和AMPA受体信号传导增加。然而，AMPA受体活性增强在酒精强化和酒精寻求行为中的机制作用尚不清楚。本研究考察了使用选择性正变构调节剂阿尼西坦增强AMPA受体功能在调节操作性酒精自我给药和线索诱导恢复中的作用。雄性酒精偏好（P-）大鼠，训练自我给药酒精（15%,v/v）与水，用阿尼西坦预处理，以评估对维持酒精自我给药的影响。为了确定强化剂的特异性，将p -大鼠训练成自我给药蔗糖（0.8%,w/v）和水，并测试阿尼西坦的效果。在接受自我给予15%酒精训练的p -大鼠中，使用反应随机线索诱导恢复程序评估了阿尼西坦在调节酒精寻求复发中的作用。相对于载体处理，阿尼西坦预处理显著增加了酒精增强反应。这种增加不归因于阿尼西坦诱导的多动，因为阿尼西坦预处理不会改变运动活动。AMPA受体的参与被证实是因为DNQX （AMPA受体拮抗剂）阻断了阿尼西坦诱导的酒精自我给药的增加。阿尼西坦没有改变糖训练的p -大鼠的糖增强反应，这表明增强的AMPA受体活性在调节酒精的增强功能方面是选择性的。最后，与对照组相比，阿尼西坦预处理增强了线索诱导的寻求酒精行为的恢复。这些数据表明，AMPA受体谷氨酸活性的增强可能是促进酒精消费和寻求最终导致酒精滥用障碍发展的行为的关键。
Long-term alcohol exposure produces neuroadaptations that contribute to the progression of alcohol abuse disorders. Chronic alcohol consumption results in strengthened excitatory neurotransmission and increased AMPA receptor signaling in animal models. However, the mechanistic role of enhanced AMPA receptor activity in alcohol reinforcement and alcohol-seeking behavior remains unclear. This study examined the role of enhanced AMPA receptor function using the selective positive allosteric modulator, aniracetam, in modulating operant alcohol self-administration and cue-induced reinstatement. Male alcohol-preferring (P-) rats, trained to self-administer alcohol (15%, v/v) versus water were pretreated with aniracetam to assess effects on maintenance of alcohol self-administration. To determine reinforcer specificity, P-rats were trained to self-administer sucrose (0.8%, w/v) versus water, and effects of aniracetam were tested. The role of aniracetam in modulating relapse of alcohol-seeking was assessed using a response-contingent cue-induced reinstatement procedure in P-rats trained to self-administer 15% alcohol. Aniracetam pretreatment significantly increased alcohol-reinforced responses relative to vehicle treatment. This increase was not attributed to aniracetam-induced hyperactivity as aniracetam pretreatment did not alter locomotor activity. AMPA receptor involvement was confirmed because DNQX (AMPA receptor antagonist) blocked the aniracetam-induced increase in alcohol self-administration. Aniracetam did not alter sucrose-reinforced responses in sucrose-trained P-rats, suggesting that enhanced AMPA receptor activity is selective in modulating the reinforcing function of alcohol. Finally, aniracetam pretreatment potentiated cue-induced reinstatement of alcohol-seeking behavior versus vehicle treated-P-rats. These data suggest that enhanced glutamate activity at AMPA receptors may be key in facilitating alcohol consumption and seeking behavior which could ultimately contribute to the development of alcohol abuse disorders.
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影响因子：
10.6
作者：
Besheer, Joyce;Grondin, Julie J. M.;Cannady, Reginald;Sharko, Amanda C.;Faccidomo, Sara;Hodge, Clyde W.
通讯作者：
Hodge, Clyde W.
影响因子：
2.9
作者：
BREESE, CR;FREEDMAN, R;LEONARD, SS
通讯作者：
LEONARD, SS
影响因子：
3.3
作者：
Gorin-Meyer, R. E.;Wiren, K. M.;Finn, D. A.
通讯作者：
Finn, D. A.
影响因子：
6
作者：
Drummond, DC
通讯作者：
Drummond, DC
影响因子：
2.3
作者：
HODGE, CW;SAMSON, HH;ERICKSON, HL
通讯作者：
ERICKSON, HL