Stress, κ manipulations, and aversive effects of ethanol in adolescent and adult male rats.
Stress, κ manipulations, and aversive effects of ethanol in adolescent and adult male rats.
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DOI：
10.1016/j.neuroscience.2012.12.028
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发表时间：
2013-09-26
期刊：
影响因子：
3.3
通讯作者：
Spear LP
中科院分区：
文献类型：
--
作者：
Anderson RI;Agoglia AE;Morales M;Varlinskaya EI;Spear LP
在青春期，一个潜在的压力发展时期，乙醇使用量增加，伴随着对乙醇相对于成年人的许多令人厌恶的影响不敏感。鉴于支持应激和κ阿片受体（KOR）系统在介导乙醇和其他药物的厌恶特性中的作用的证据，本研究评估了去甲阿托啡亚胺（nor-BNI）对乙醇诱导的条件性味觉厌恶（CTA）的KOR拮抗作用。（暴露于重复约束）和非应激雄性大鼠（实验1），其中一半的大鼠在应激暴露之前用nor-BNI预处理。在实验2中，还比较了压力和非压力青少年和成人中由κ激动剂U62，066诱导的CTA。一个非常可口的解决方案（巧克力Boost）被用作条件刺激（CS），从而避免了水剥夺，以激励消费的CS在条件反射。没有发现乙醇诱导的CTA的压力的影响，所有剂量引起厌恶的青少年和成年人在这两种压力条件。然而，在强调的主题，成年人给予nor-BNI之前，重复的压力显示迟钝的乙醇厌恶相对于成年人给予生理盐水在那个时候。在青少年中未观察到nor-BNI的这种作用，研究结果支持KOR参与乙醇CTA在强调青少年和成人中的不同作用。实验2的结果表明，所有剂量的U62，066引起的厌恶在两个年龄的非应激动物中被减弱，在应激动物中，研究结果支持应激在KOR激活的厌恶效应中的调节作用。总的来说，这些结果表明，尽管应激受试者的KOR敏感性似乎降低，但在目前的测试情况下，该受体系统似乎不会导致乙醇诱导的CTA的年龄差异。
Elevated ethanol use during adolescence, a potentially stressful developmental period, is accompanied by insensitivity to many aversive effects of ethanol relative to adults. Given evidence that supports a role for stress and the kappa opioid receptor (KOR) system in mediating aversive properties of ethanol and other drugs, the present study assessed the role of KOR antagonism by norbinaltorphimine (nor-BNI) on ethanol-induced conditioned taste aversion (CTA) in stressed (exposed to repeated restraint) and non-stressed male rats (Experiment 1), with half of the rats pretreated with nor-BNI before stressor exposure. In Experiment 2, CTA induced by the kappa agonist U62,066 was also compared in stressed and non-stressed adolescents and adults. A highly palatable solution (chocolate Boost) was used as the conditioned stimulus (CS), thereby avoiding the need for water deprivation to motivate consumption of the CS during conditioning. No effects of stress on ethanol-induced CTA were found, with all doses eliciting aversions in adolescents and adults in both stress conditions. However, among stressed subjects, adults given nor-BNI before the repeated stressor displayed blunted ethanol aversion relative to adults given saline at that time. This effect of nor-BNI was not seen in adolescents, findings that support a differential role for the KOR involvement in ethanol CTA in stressed adolescents and adults. Results from Experiment 2 revealed that all doses of U62,066 elicited aversions in non-stressed animals of both ages that were attenuated in stressed animals, findings that support a modulatory role for stress in aversive effects of KOR activation. Collectively, these results suggest that although KOR sensitivity appears to be reduced in stressed subjects, this receptor system does not appear to contribute to age differences in ethanol-induced CTA under the present test circumstances.
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