Reinstatement of ethanol and sucrose seeking by the neurosteroid allopregnanolone in C57BL/6 mice.
Reinstatement of ethanol and sucrose seeking by the neurosteroid allopregnanolone in C57BL/6 mice.
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DOI：
10.1007/s00213-008-1303-8
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发表时间：
2008-12
影响因子：
3.4
通讯作者：
Ford MM
中科院分区：
文献类型：
--
作者：
Finn DA;Mark GP;Fretwell AM;Gililland-Kaufman KR;Strong MN;Ford MM
我们实验室最近的工作证明，在雄性C57 BL/6小鼠中，操作性乙醇自我给药的“吸管”方法产生了高乙醇摄入量和血液乙醇浓度，以及在非强化条件下响应的典型消光“爆发”。然而，尚未在小鼠中用该模型检查消退后恢复反应的神经化学基础。基于GABA能神经甾体别孕烯醇酮（ALLO）显著增加乙醇自我给药的完成阶段的发现，本研究确定了ALLO对恢复已熄灭的乙醇寻求行为的影响，并将这种影响与恢复对蔗糖奖励的反应进行了比较。训练单独的雄性C57 BL/6小鼠组以使用杠杆按压10%乙醇（10 E）或5%蔗糖（5S）溶液。在活动杆上按下16次（RR 16）的单次响应要求导致30分钟连续接触10 E或5S溶液。在动物对RR 16时间表反应14周后，将小鼠暴露于30分钟的消退期，其中反应没有预定的后果。一旦反应稳定在消退前基线以下，小鼠在受试者内设计中在消退期之前15分钟接受ALLO（0、3.2、5.6、10或17 mg/kg）的IP注射。在10 E和5S组中，在非增强条件下，ALLO产生了剂量依赖性的反应增加。额外的工作记录了条件提示光或复合提示（光+杠杆缩回）恢复先前活动杠杆上的非强化反应的能力。这些发现明确表明，条件提示和启动与ALLO是有效的刺激恢复乙醇和蔗糖寻求行为的C57 BL/6小鼠。
Recent work in our laboratory documented that the “sipper” method of operant ethanol self-administration produced high ethanol intake and blood ethanol concentrations as well as the typical extinction “burst” in responding under non-reinforced conditions in male C57BL/6 mice. However, the neurochemical basis for reinstatement of responding following extinction has not been examined in mice with this model. Based on findings that the GABAergic neurosteroid allopregnanolone (ALLO) significantly increased the consummatory phase of ethanol self-administration, the present study determined the effect of ALLO on reinstatement of extinguished ethanol-seeking behavior and compared this effect to reinstatement of responding for sucrose reward. Separate groups of male C57BL/6 mice were trained to lever press for access to a 10% ethanol (10E) or a 5% sucrose (5S) solution. A single response requirement of 16 presses (RR16) on an active lever resulted in 30 min of continuous access to the 10E or 5S solution. After the animals responded on the RR16 schedule for 14 weeks, mice were exposed to 30 min extinction sessions where responding had no scheduled consequence. Once responding stabilized below the pre-extinction baseline, mice received an IP injection of ALLO (0, 3.2, 5.6, 10 or 17 mg/kg) 15 min prior to the extinction session in a within-subjects design. ALLO produced a dose-dependent increase in responding under non-reinforced conditions in both the 10E and 5S groups. Additional work documented the ability of a conditioned cue light or a compound cue (light+lever retraction) to reinstate non-reinforced responding on the previously active lever. These findings definitively show that conditioned cues and priming with ALLO are potent stimuli for reinstating both ethanol and sucrose seeking behavior in C57BL/6 mice.