Stress alters social behavior and sensitivity to pharmacological activation of kappa opioid receptors in an age-specific manner in Sprague Dawley rats.
Stress alters social behavior and sensitivity to pharmacological activation of kappa opioid receptors in an age-specific manner in Sprague Dawley rats.
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DOI：
10.1016/j.ynstr.2018.09.003
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发表时间：
2018-11
影响因子：
5
通讯作者：
Diaz MR
中科院分区：
文献类型：
--
作者：
Varlinskaya EI;Spear LP;Diaz MR
运动啡/阿片受体（DYN/KOR）系统已被确定为应激的主要目标，这是由于该系统的激活引起的行为影响，如烦躁不安、厌恶和焦虑样改变。DYN/KOR系统中的许多适应性也被确定为对压力的反应。然而，尽管大多数检查DYN/KOR系统功能的研究都是在成年啮齿动物中进行的，但越来越多的证据表明该系统是受个体遗传学调节的。同样，暴露于压力的结果也因个体发育而异。基于这些发育相似性，本研究的目的是系统地测试一种选择性KOR激动剂U-62066对非应激雄性和雌性大鼠以及有重复约束史的雄性和雌性大鼠（90 分钟/天，5次暴露）在个体发育过程中社会行为的各个方面的影响。我们发现，重复约束的社会后果随着年龄的变化而不同：青少年压力导致游戏打架的显著增加，而青少年和成人压力导致社会调查和社会偏好的减少。KOR激动剂U-62066的剂量依赖性降低了无压力成年鼠的社会行为，在测试的最高剂量下产生社会回避，而年轻的动物对U-62066的这种社会抑制作用的敏感性降低。有趣的是，在应激动物中，KOR激动剂的社会抑制作用在所有年龄段都被减弱，青少年和青少年对特定剂量的U-62066表现出更大的社会偏好。综上所述，这些发现支持了DYN/KOR系统随年龄变化的假设，并且在发育过程中对压力的反应和适应存在差异。
The dynorphin/kappa opioid receptor (DYN/KOR) system has been identified as a primary target of stress due to behavioral effects, such as dysphoria, aversion, and anxiety-like alterations that result from activation of this system. Numerous adaptations in the DYN/KOR system have also been identified in response to stress. However, whereas most studies examining the function of the DYN/KOR system have been conducted in adult rodents, there is growing evidence suggesting that this system is ontogenetically regulated. Likewise, the outcome of exposure to stress also differs across ontogeny. Based on these developmental similarities, the objective of this study was to systematically test effects of a selective KOR agonist, U-62066, on various aspects of social behavior across ontogeny in non-stressed male and female rats as well as in males and females with a prior history of repeated exposure to restraint (90 min/day, 5 exposures). We found that the social consequences of repeated restraint differed as a function of age: juvenile stress produced substantial increases in play fighting, whereas adolescent and adult stress resulted in decreases in social investigation and social preference. The KOR agonist U-62066 dose-dependently reduced social behaviors in non-stressed adults, producing social avoidance at the highest dose tested, while younger animals displayed reduced sensitivity to this socially suppressing effect of U-62066. Interestingly, in stressed animals, the socially suppressing effects of the KOR agonist were blunted at all ages, with juveniles and adolescents exhibiting increased social preference in response to certain doses of U-62066. Taken together, these findings support the hypothesis that the DYN/KOR system changes with age and differentially responds and adapts to stress across development.
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影响因子：
3.4
作者：
BALSKUBIK, R;HERZ, A;SHIPPENBERG, TS
通讯作者：
SHIPPENBERG, TS
影响因子：
0.7
作者：
Alexeeva, E. V.;Nazarova, G. A.;Sudakov, S. K.
通讯作者：
Sudakov, S. K.
影响因子：
4.1
作者：
Horovitz, O.;Tsoory, M. M.;Richter-Levin, G.
通讯作者：
Richter-Levin, G.
早期压力作为酒精和药物依赖性的预测因素。
影响因子：
3.4
作者：
Enoch, Mary-Anne
通讯作者：
Enoch, Mary-Anne
影响因子：
3.4
作者：
Anderson, Rachel I.;Morales, Melissa;Spear, Linda P.;Varlinskaya, Elena I.
通讯作者：
Varlinskaya, Elena I.