Drug challenges reveal differences in mediation of stress facilitation of voluntary alcohol drinking and withdrawal-induced anxiety in alcohol-preferring P rats.
Drug challenges reveal differences in mediation of stress facilitation of voluntary alcohol drinking and withdrawal-induced anxiety in alcohol-preferring P rats.
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药物挑战揭示了偏好酒精的 P 大鼠在自愿饮酒的应激促进和戒断诱发的焦虑之间的调节差异。
DOI：
10.1111/j.1530-0277.2007.00445.x
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Breese,GeorgeR
中科院分区：
文献类型：
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作者：
Overstreet,DavidH;Knapp,DarinJ;Breese,GeorgeR
背景：关于暴露于压力是否会加速复发和/或增加酒精（乙醇）摄入量存在争议。我们的实验室已经证明，在短暂被迫暴露于酒精中之前，反复的压力会导致戒断诱导的焦虑样行为。由于焦虑通常被认为是酗酒复发的诱因，我们决定检查的后果，强调酒精偏好P大鼠自愿饮酒和戒断诱导anxiety.Methods：P大鼠进行3个周期的5天自愿饮酒和2天的剥夺。 在第一次和第二次剥夺/撤药期间（4 h），对一些动物施加束缚应激（60 min）。 药物（氟马西尼，丁螺环酮，SB 242，084，CP 154，526，CRA 1000，纳洛酮，氟哌啶醇，奥氮平，纳洛酮，氟哌啶醇）给一些大鼠30分钟前restraint stress.Results：强调，剥夺P大鼠表现出更长的持续时间的饮酒量增加和焦虑样行为的社会互动测试后，自愿饮酒的第三个周期后退出。 在每次束缚应激前给予苯二氮卓类受体拮抗剂氟马西尼（5 mg/kg）、促肾上腺皮质激素释放因子受体拮抗剂CRA 1000（3 mg/kg）和CP 154，526（10 mg/kg）、5-HT 1A受体部分激动剂丁螺环酮（0.6 mg/kg）和混合5-HT 2C/D2受体拮抗剂奥氮平，可有效减少饮酒量增加的持续时间和戒断诱导的焦虑样行为。 相反，虽然阿片受体拮抗剂纳洛酮（20 mg/kg），5-HT 2C受体拮抗剂SB 242084（3 mg/kg），和多巴胺受体拮抗剂氟哌啶醇（0.1 mg/kg）也减少饮酒，他们没有显着改变焦虑样behavior.Conclusion：这些结果表明，应激诱导的促进饮酒和戒断诱导的焦虑样行为在P大鼠可能是密切的，但不完全联系。
Background:There is controversy over whether exposure to stress precipitates relapse and/or increases alcohol (ethanol) intake. Our laboratory has demonstrated that repeated stress prior to withdrawal from a brief forced exposure to alcohol results in withdrawal‐induced anxiety‐like behavior. Because anxiety is often regarded as a precipitating factor in relapsing alcoholics, we decided to examine the consequences of stressing alcohol‐preferring P rats on both voluntary alcohol drinking and withdrawal‐induced anxiety.Methods:P rats were subjected to 3 cycles of 5 days of voluntary alcohol drinking and 2 days of deprivation. Restraint stress (60 min) was applied to some animals during the first and second deprivations/withdrawals (at 4 h). Drugs (flumazenil, buspirone, SB242,084, CP154,526, CRA1000, naloxone, haloperidol, olanzapine, naloxone, and haloperidol) were given to some rats 30 min prior to restraint stress.Results:Stressed, deprived P rats exhibited both a longer duration of elevated alcohol drinking and anxiety‐like behavior in the social interaction test upon withdrawal after the third cycle of voluntary alcohol drinking. When given prior to each of the restraint stresses, the benzodiazepine receptor antagonist flumazenil (5 mg/kg), the corticotrophin releasing factor receptor antagonists CRA1000 (3 mg/kg) and CP154,526 (10 mg/kg), the serotonin 5‐HT1Areceptor partial agonist buspirone (0.6 mg/kg), and the mixed 5‐HT2C/D2 receptor antagonist olanzapine were effective in reducing the increased duration of elevated alcohol drinking and the withdrawal‐induced anxiety‐like behavior. In contrast, while the opiate receptor antagonist naloxone (20 mg/kg), the 5‐HT2Creceptor antagonist SB242084 (3 mg/kg), and the dopamine receptor antagonist haloperidol (0.1 mg/kg) also reduced drinking, they did not significantly alter anxiety like behavior.Conclusion:These results suggest that stress‐induced facilitation of alcohol drinking and withdrawal‐induced anxiety‐like behavior in P rats may be closely but imperfectly linked.