Effect of σ₁ receptor antagonism on ethanol and natural reward seeking.
Effect of σ₁ receptor antagonism on ethanol and natural reward seeking.
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DOI：
10.1097/wnr.0b013e32835717c8
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发表时间：
2012-10-03
期刊：
影响因子：
1.7
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中科院分区：
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Sigma-1受体与认知功能、焦虑、抑郁和应激反应的调节有关。此外，σ1受体已被证明参与精神兴奋剂的行为和动机效应。最近的研究表明，σ1受体拮抗剂可以防止乙醇诱导的小鼠条件位置偏好和酒精依赖或酒精偏好大鼠的过度饮酒。因此，本研究旨在通过动物复发模型确定σ1受体的这种作用是否延伸到乙醇寻求行为，并测试强效σ1受体拮抗剂BD1047的抑制作用是否推广到自然的奖励寻求行为。两组大鼠分别接受训练，在鉴别刺激（S+）存在的情况下，自我口服10% （w/v）乙醇或高度可口的强化物，3%/0.125% （w/v）葡萄糖/糖精（SuperSac）。在消光后，在此期间，增强剂和S+被保留，乙醇或SuperSac S+的呈现产生了相当的反应恢复。BD1047 （1-20 mg/kg）对乙醇S+-和SuperSac S+-诱导的恢复均产生相似的行为效应，只有在最高剂量BD1047时才能预防条件恢复。结果表明，在当前条件下，σ1受体阻断对乙醇刺激和supersac刺激诱导的条件恢复产生相似的影响，提示控制乙醇和自然奖励寻求的神经机制重叠。
Sigma-1 (σ1) receptors have been implicated in cognitive function, anxiety, depression, and the regulation of stress responses. Additionally, σ1 receptors have been shown to participate in the behavioral and motivational effects of psychostimulants. Recent studies have demonstrated that σ1 receptor antagonism prevents ethanol-induced conditioned place preference in mice and excessive drinking in alcohol-dependent or alcohol-preferring rats. Therefore, this study was designed to determine whether this role for σ1 receptors extends to ethanol-seeking behavior using an animal model of relapse and tested whether the suppressant effect of a potent σ1 receptor antagonist, BD1047, generalizes to natural reward-seeking behavior. Two separate groups of rats were trained to orally self-administer 10% (w/v) ethanol or a highly palatable reinforcer, 3%/0.125% (w/v) glucose/saccharin (SuperSac), in the presence of a discriminative stimulus (S+). Following extinction, during which the reinforcers and S+ were withheld, the presentation of the ethanol or SuperSac S+ produced comparable recovery of responding. BD1047 (1–20 mg/kg) produced similar behavioral effects on both ethanol S+- and SuperSac S+-induced reinstatement, with prevention of conditioned reinstatement only at the highest BD1047 dose. The present results show that σ1 receptor blockade under the present conditions produces similar effects on conditioned reinstatement induced by ethanol- and SuperSac-related stimuli, suggestive of overlapping neural mechanisms that control ethanol and natural reward seeking.