D-环丝氨酸对小鼠觅酒行为消退和再条件反射的影响。
Effects of D-cycloserine on extinction and reconditioning of ethanol-seeking behavior in mice.
机构信息
Department of Behavioral Neuroscience and Portland Alcohol Research Center, Oregon Health & Science University, Portland, Oregon.
出版信息
Alcohol Clin Exp Res. 2009 May;33(5):772-82. doi: 10.1111/j.1530-0277.2009.00895.x. Epub 2009 Mar 6.
BACKGROUND
D-cycloserine (DCS), a partial N-methyl-D-aspartate receptor agonist, has been shown to enhance the extinction of both cocaine and amphetamine-induced conditioned place preference (CPP). However, there have been no reports of the effects of DCS on the extinction of ethanol-conditioned behaviors in mice. Thus, the current experiments examined the effects of DCS on the extinction and subsequent reconditioning of ethanol-induced CPP in mice.
METHODS
Male DBA/2J mice received either 2 or 4 pairings of ethanol (2 g/kg) with a conditioned stimulus (CS+) floor cue (and an equal number of saline pairings with a CS- floor cue on alternate days) resulting in either a weak or strong ethanol CPP, respectively. Following conditioning of a strong ethanol CPP mice received saline or 30 mg/kg DCS prior to each of the twelve 30-minute choice extinction trials administered at 48-hour intervals. Mice that had received conditioning of a weak ethanol CPP received saline, 30 or 60 mg/kg DCS immediately before each of the six 30-minute choice extinction trials. Following successful ethanol CPP extinction, mice received reconditioning trials similar to the initial conditioning trials. A final experiment examined the effects 12 DCS pre-exposures (15, 30, and 60 mg/kg) on initial conditioning of ethanol CPP.
RESULTS
First, we showed that 2 doses of DCS (30 and 60 mg/kg) did not have aversive properties that could confound the effects on extinction of CPP (Experiment 1). Second, we showed that DCS (30 and 60 mg/kg) had no effect on the rate of extinction of either strong (Experiment 2) or weak (Experiment 3) ethanol-induced CPP. Interestingly, DCS administered during extinction interfered with reconditioning of ethanol-induced CPP--an effect specific to reconditioning, as DCS pre-exposure did not influence initial ethanol CPP conditioning (Experiment 4).
CONCLUSIONS
These experiments show that although DCS showed no effect on extinction behavior, when given during extinction it interfered with subsequent reconditioning of ethanol CPP. The mechanisms of this effect were not, however, due to nonspecific interference with learning because repeated DCS pre-exposures did not impair initial conditioning of ethanol CPP.
背景
D-环丝氨酸（DCS）是一种部分 N-甲基-D-天冬氨酸受体激动剂，已被证明可以增强可卡因和安非他命诱导的条件性位置偏爱（CPP）的消退。然而，目前还没有报道 DCS 对小鼠乙醇条件行为消退的影响。因此，本实验研究了 DCS 对小鼠乙醇诱导的 CPP 消退和随后再条件作用的影响。
方法
雄性 DBA/2J 小鼠接受 2 或 4 次乙醇（2 g/kg）与条件刺激（CS+）地板线索配对（隔日接受等量盐水配对与 CS-地板线索配对），分别导致弱或强乙醇 CPP。在强乙醇 CPP 条件作用后，小鼠在每 48 小时进行的 12 次 30 分钟选择消退试验前接受盐水或 30mg/kg DCS。在弱乙醇 CPP 条件作用后，接受盐水、30 或 60mg/kg DCS 的小鼠，在每次 30 分钟的选择消退试验前立即接受 6 次。成功消退乙醇 CPP 后，小鼠接受类似于初始条件作用试验的再条件作用试验。最后的实验研究了 12 次 DCS 预暴露（15、30 和 60mg/kg）对初始乙醇 CPP 条件作用的影响。
结果
首先，我们发现 2 种剂量的 DCS（30 和 60mg/kg）没有产生可能混淆 CPP 消退的厌恶性质（实验 1）。其次，我们发现 DCS（30 和 60mg/kg）对强（实验 2）或弱（实验 3）乙醇诱导的 CPP 的消退率没有影响。有趣的是，在消退期间给予 DCS 会干扰乙醇诱导的 CPP 的再条件作用——这种作用是特异性的再条件作用，因为 DCS 预暴露不会影响初始乙醇 CPP 条件作用（实验 4）。
结论
这些实验表明，尽管 DCS 对消退行为没有影响，但在消退期间给予时，它会干扰随后的乙醇 CPP 再条件作用。然而，这种作用的机制不是由于对学习的非特异性干扰，因为重复的 DCS 预暴露不会损害初始乙醇 CPP 的条件作用。
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