Ethanol-induced conditioned place preference, but not aversion, is blocked by treatment with D-penicillamine, an inactivation agent for acetaldehyde
Ethanol-induced conditioned place preference, but not aversion, is blocked by treatment with D-penicillamine, an inactivation agent for acetaldehyde
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DOI：
10.1007/s00213-005-0224-z
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发表时间：
2006-01-01
影响因子：
3.4
通讯作者：
Miquel, M
中科院分区：
文献类型：
--
作者：
Font, L;Aragon, CMG;Miquel, M
理性：有证据表明乙醛参与了乙醇寻求行为和奖励的控制。D-青霉胺是一种巯基氨基酸，是一种高度选择性的乙醛灭活剂。本实验室先前的研究表明，D-青霉胺可防止乙醇引起的行为刺激和乙酰丙酮引起的小鼠运动抑制。目的：乙醇衍生的乙醛对乙醇的情感效应（偏好和厌恶）的贡献进行了评估，使用无偏的位置调节设计。研究方法：雄性小鼠接受四对独特的地板刺激（CS+：GRID+或HOLE+），并在暴露于位置调节装置5分钟之前（偏好）或之后（厌恶）注射盐水和乙醇（2 g/kg）。提供了与隔日盐水-盐水注射相关的不同地板刺激（CS-：网格-或孔-）。对于不同组的动物，与CS+的配对与盐水和乙醇注射相关，但在隔日，它们接受D-青霉胺（50或75 mg/kg）和乙醇注射与CS-地板刺激配对。在最后一次调节试验后24 h进行60 min偏好测试。按照类似的程序测试D-青霉胺对吗啡（16 mg/kg）和可卡因（20 mg/kg）诱导的条件性位置偏爱（CPP）的影响。结果：乙醇可引起CPP和条件性位置厌恶（CPA），而D-青霉胺仅阻断CPP。D-青霉胺本身既不产生奖励作用，也不产生厌恶作用。吗啡和可卡因的CPP观察不受D-青霉胺预处理。结论：本研究的结果表明，乙醛的选择性失活阻断了奖励，但不厌恶，乙醇的影响和支持的作用，乙醇的情感特性的乙醇代谢产物。
Rational: There is evidence to suggest that acetaldehyde is involved in the control of ethanol-seeking behavior and reward. D-penicillamine, a thiol amino acid, is a highly selective agent for the inactivation of acetaldehyde. Previous studies from our laboratory have demonstrated that D-penicillamine prevents both behavioral stimulation induced by ethanol and acetaldehyde-produced locomotor depression in mice. Objectives: The contribution of ethanol-derived acetaldehyde to the affective effects of ethanol (preference and aversion) was assessed using an unbiased place conditioning design. Methods: Male mice received four pairings of a distinctive floor stimulus (CS+: GRID+ or HOLE+) with injections of saline and ethanol (2 g/kg) given before (preference) or after (aversion) the 5-min exposure to the place conditioning apparatus. A different floor stimulus (CS-: GRID- or HOLE-), associated with saline-saline injections on alternate days, was presented. For a different group of animals, the pairings with the CS+ were associated with saline and ethanol injections, but on alternate days, they received D-penicillamine (50 or 75 mg/kg) and ethanol injections paired with the CS-floor stimulus. A 60-min preference test was carried out 24 h after the last conditioning trial. A similar procedure was followed to test the effect of D-penicillamine on morphine (16 mg/kg) and cocaine-induced (20 mg/kg) conditioned place preference (CPP). Results: CPP and conditioned place aversion (CPA) were observed for ethanol, but D-penicillamine only blocked CPP. D-penicillamine, by itself, did not produce either rewarding or aversive effects. CPP observed for morphine and cocaine was unaffected by D-penicillamine pretreatment. Conclusions: The results of the present study suggest that the selective inactivation of acetaldehyde blocked the rewarding, but not aversive, effects of ethanol and support the role of this ethanol metabolite in the affective properties of ethanol.