Exposure to histone deacetylase inhibitors during Pavlovian conditioning enhances subsequent cue-induced reinstatement of operant behavior.
Exposure to histone deacetylase inhibitors during Pavlovian conditioning enhances subsequent cue-induced reinstatement of operant behavior.
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在巴甫洛夫调节过程中暴露于组蛋白脱乙酰酶抑制剂会增强随后的提示诱导的操作行为的恢复。
DOI：
10.1097/fbp.0b013e32836104ea
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发表时间：
2013
影响因子：
1.6
通讯作者：
Kippin,TodE
中科院分区：
文献类型：
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作者：
Ploense,KyleL;Kerstetter,KerryA;Wade,MatthewA;Woodward,NicholasC;Maliniak,Dan;Reyes,Michael;Uchizono,RussellS;Bredy,TimothyW;Kippin,TodE
组蛋白去乙酰化酶抑制剂（HDACIs）增强恐惧条件反射和可卡因诱导的条件性位置偏好后的记忆。在这里，我们研究了两种非特异性hdac，丙戊酸（VPA）和丁酸钠（NaB）对条件刺激（CS）诱导的操作性反应恢复的食欲学习的影响。训练大鼠杠杆按压以增强食物，然后注射VPA (50-200 mg/kg, ip), NaB （250-1000 mg/kg, ip）或生理盐水（1.0 ml/kg）， 2小时后接受配对的非偶然呈现食物颗粒，之前是音调+光提示CS。随后，大鼠进行了操作性反应的消失，随后进行了反应偶然性的再暴露于CS。在条件反射前给予VPA （100 mg/kg）或NaB （1000 mg/kg）的大鼠比生理盐水对照组表现出明显更高的线索诱导恢复。在给予食物颗粒和CS之间的随机关系下，在条件训练之前接受车辆或VPA （100 mg/kg）的大鼠未能表现出随后的线索诱导恢复，两组之间没有差异。这些发现表明，在某些情况下，hdac通过特别增加CS的联想强度来加强记忆形成，而不是通过增加寻求强化的动机。
Histone deacetylase inhibitors (HDACIs) strengthen memory following fear conditioning and cocaine-induced conditioned place preference. Here, we examined the effects of two nonspecific HDACIs, valproic acid (VPA) and sodium butyrate (NaB), on appetitive learning measured by conditioned stimulus (CS)-induced reinstatement of operant responding. Rats were trained to lever press for food reinforcement and then injected with VPA (50–200 mg/kg, ip), NaB (250–1000 mg/kg, ip), or saline vehicle (1.0 ml/kg), 2 h before receiving pairings of noncontingent presentation of food pellets preceded by a tone+ light cue CS. Rats next underwent extinction of operant responding followed by response-contingent re-exposure to the CS. Rats receiving VPA (100 mg/kg) or NaB (1000 mg/kg) before conditioning displayed significantly higher cue-induced reinstatement than did saline controls. Rats that received either vehicle or VPA (100 mg/kg) before a conditioning session with a randomized relation between presentation of food pellets and the CS failed to show subsequent cue-induced reinstatement with no difference between the two groups. These findings indicate that, under certain contexts, HDACIs strengthen memory formation by specifically increasing the associative strength of the CS, not through an increasing motivation to seek reinforcement.