Ethanol reward and aversion in mice bred for sensitivity to ethanol withdrawal
Ethanol reward and aversion in mice bred for sensitivity to ethanol withdrawal
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DOI：
10.1097/00000374-199804000-00025
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发表时间：
1998-04-01
影响因子：
3.2
通讯作者：
Cunningham, CL
中科院分区：
文献类型：
--
作者：
Chester, JA;Risinger, FO;Cunningham, CL
本研究考察了选择性培育的对酒精戒断敏感的小鼠的条件性位置偏爱(CPP)和条件性味觉厌恶(CTA)范式的差异。选用易戒断(WSP)和耐戒断(WSR)小鼠以及高酒精戒断(HAW)和低酒精戒断(LAW)小鼠，分别选择慢性酒精戒断和急性酒精戒断。在CPP实验中，雄性HAW和Law(第5代)小鼠接受乙醇配对(2g/kg)，并有独特的地板刺激。在中间的几天里，小鼠接受了生理盐水和另一种地板类型的配对。在偏好测试期间，所有小鼠在进入浴池地板类型的60分钟之前都接受了生理盐水注射。山鸦鼠表现出对乙醇配对地板的条件性偏好，而法律鼠则没有。在CTA实验中，雄性HAW、LAW、WSP和WSR小鼠适应2小时/天的限水方案，随后在接触氯化钠口味的溶液1小时后立即接受乙醇注射(0、2、2.5或4g/kg，ip)。盐摄入量的剂量依赖性减少反映了HAW/LAW和WSP/WSR品系的CTA的发展。然而，在第一次乙醇-氯化钠配对后，WSP小鼠相对于WSR小鼠观察到较小的CTA。在随后的条件反射试验中，WSP/WSR小鼠表现出类似的氯化钠摄入量减少。总体而言，这些数据表明，HAW小鼠被选择性地培育为对急性乙醇戒断高度敏感，在CPP范式中对乙醇的奖赏效应更敏感。这一结果与之前的一项研究一致，该研究表明WSP小鼠的CPP比WSR小鼠更大。在CTA范式中，在HAW/Law选择的品系中，对乙醇戒断的敏感性似乎与对乙醇的厌恶特性的敏感性没有遗传相关性。然而，WSP/WSR品系获得CTA的差异表明，一些决定乙醇戒断严重程度的基因也可能影响对乙醇厌恶效应的初始敏感性。
The present study examined mice selectively bred for sensitivity to ethanol withdrawal for differences in the conditioned place preference (CPP) and conditioned taste aversion (CTA) paradigms. Withdrawal Seizure-Prone (WSP) and Withdrawal Seizure-Resistant (WSR) mice and High Alcohol Withdrawal (HAW) and Low Alcohol Withdrawal (LAW) mice were selectively bred for differences in chronic and acute ethanol withdrawal, respectively. For the CPP experiment, male HAW and LAW (generation 5) mice received Tour pairings of ethanol (2 g/kg), with a distinctive floor stimulus. On intervening days, mice received saline paired with an alternate floor type. During the preference test, all mice received an injection of saline before 60-min access to bath floor types. HAW mice showed conditioned preference for the ethanol-paired floor, whereas LAW mice did not. For the CTA experiments, male HAW, LAW, WSP, and WSR mice were adapted to a 2-hr/day water restriction regimen and subsequently received ethanol injections (0, 2, 2.5, or 4 g/kg, ip) immediately after 1-hr access to a NaCl-flavored solution. Dose-dependent reductions in NaCl intake reflected the development of CTA in both HAW/LAW and WSP/WSR lines. However, a smaller magnitude of CTA was observed in WSP mice relative to WSR mice after the first ethanol-NaCl pairing. WSP/WSR mice showed similar reductions of NaCl intake on subsequent conditioning trials. Overall, these data suggest that HAW mice selectively bred for high sensitivity to acute ethanol withdrawal are more sensitive to the rewarding effects of ethanol in the CPP paradigm. This outcome is consistent with a previous study showing greater CPP in WSP mice relative to,WSR mice. In the CTA paradigm, sensitivity to ethanol withdrawal in the HAW/LAW selected lines does not appear to be genetically correlated with sensitivity to the aversive properties of ethanol. However, the difference in acquisition of CTA in WSP/WSR lines suggest that some genes determining ethanol withdrawal severity may also influence initial sensitivity to ethanol's aversive effects.