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乙醇暴露对线索性和情境性恐惧条件反射及消退的影响因青春期或成年期暴露的时间不同而有所差异。

Consequences of ethanol exposure on cued and contextual fear conditioning and extinction differ depending on timing of exposure during adolescence or adulthood.

作者信息

Broadwater Margaret, Spear Linda P

机构信息

Center for Development and Behavioral Neuroscience, Department of Psychology, Binghamton University, Binghamton, NY 13902-6000, United States.

出版信息

Behav Brain Res. 2013 Nov 1;256:10-9. doi: 10.1016/j.bbr.2013.08.013. Epub 2013 Aug 9.

Abstract

Some evidence suggests that adolescents are more sensitive than adults to ethanol-induced cognitive deficits and that these effects may be long-lasting. The purpose of Exp 1 was to determine if early-mid adolescent [postnatal day (P) 28-48] intermittent ethanol exposure would affect later learning and memory in a Pavlovian fear conditioning paradigm differently than comparable exposures in adulthood (P70-90). In Exp 2 animals were exposed to ethanol during mid-late adolescence (P35-55) to assess whether age of initiation within the adolescent period would influence learning and memory differentially. Male Sprague-Dawley rats were given 4 g/kg i.g. ethanol (25%) or water every 48 h for a total of 11 exposures. After a 22 day non-ethanol period, animals were fear conditioned to a context (relatively hippocampal-dependent task) or tone (amygdala-dependent task), followed by retention tests and extinction (mPFC-dependent) of this conditioning. Despite similar acquisition, a deficit in context fear retention was evident in animals exposed to ethanol in early adolescence, an effect not observed after a comparable ethanol exposure in mid-late adolescence or adulthood. In contrast, animals that were exposed to ethanol in mid-late adolescence or adulthood showed enhanced resistance to context extinction. Together these findings suggest that repeated ethanol imparts long-lasting consequences on learning and memory, with outcomes that differ depending on age of exposure. These results may reflect differential influence of ethanol on the brain as it changes throughout ontogeny and may have implications for alcohol use not only throughout the developmental period of adolescence, but also in adulthood.

摘要

一些证据表明,青少年比成年人对乙醇诱导的认知缺陷更敏感,而且这些影响可能是长期的。实验1的目的是确定青春期早期至中期(出生后第28 - 48天)间歇性乙醇暴露是否会对巴甫洛夫恐惧条件反射范式中的后期学习和记忆产生与成年期(第70 - 90天)类似暴露不同的影响。在实验2中,动物在青春期中期至后期(第35 - 55天)暴露于乙醇,以评估青春期内开始暴露的年龄是否会对学习和记忆产生不同影响。给雄性Sprague-Dawley大鼠每48小时腹腔注射4 g/kg乙醇(25%)或水,共注射11次。在22天的非乙醇期后,对动物进行恐惧条件反射训练,使其适应一种环境(相对依赖海马体的任务)或音调(依赖杏仁核的任务),随后进行该条件反射的记忆测试和消退(依赖内侧前额叶皮质)。尽管习得情况相似,但青春期早期暴露于乙醇的动物在环境恐惧记忆方面存在明显缺陷,而在青春期中期至后期或成年期进行类似乙醇暴露后未观察到这种效应。相反,青春期中期至后期或成年期暴露于乙醇的动物对环境消退表现出更强的抵抗力。这些发现共同表明,反复接触乙醇会对学习和记忆产生长期影响,其结果因暴露年龄而异。这些结果可能反映了乙醇在个体发育过程中大脑变化时对大脑的不同影响,不仅对青春期整个发育阶段的酒精使用有影响,对成年期也有影响。

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