Consequences of Adolescent Exposure to the Cannabinoid Receptor Agonist WIN55,212-2 on Working Memory in Female Rats.
Consequences of Adolescent Exposure to the Cannabinoid Receptor Agonist WIN55,212-2 on Working Memory in Female Rats.
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DOI：
10.3389/fnbeh.2017.00137
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发表时间：
2017
影响因子：
3
通讯作者：
Torregrossa MM
中科院分区：
文献类型：
--
作者：
Kirschmann EK;McCalley DM;Edwards CM;Torregrossa MM
大麻是青少年普遍使用的非法物质，多项研究表明，青少年吸食大麻会导致长期认知缺陷，包括注意力和记忆力问题。然而，临床前动物研究观察青春期接触大麻素后的认知缺陷，实验者给予的大麻素剂量可能超过生物体选择服用的剂量，这表明意外事件和剂量是大麻素暴露后果转化模型中需要解决的关键因素。事实上，我们最近在雄性大鼠中开发了一种青少年大麻素自我给药范例，并发现先前青少年自我给药大麻素受体激动剂 WIN55,212-2 (WIN) 可以改善成年期的工作记忆表现。此外，自行服用的剂量并不像被发现会产生记忆缺陷的剂量那么高。然而，考虑到药物自我给药以及学习和记忆过程中已知的性别差异，大麻素自我给药可能会对女性产生不同的认知后果。因此，我们的目的是探讨青春期雌性大鼠自行给药与实验者给药 WIN 对成年认知功能的影响。训练雌性大鼠在整个青春期（出生后第 34-59 天）每天自我施用 WIN。对照组自行管理车辆解决方案。最终 SA 疗程后 24 小时使用短期空间记忆测试来确定青少年 WIN 自我管理对记忆的急性影响；并使用延迟匹配样本工作记忆任务评估了成年期长期禁欲期间对认知表现的长期影响。在一项单独的实验中，女性每天腹腔（IP）注射低剂量或高剂量的 WIN，分别对应于自我给药剂量和典型实验者给药剂量，或者在青春期使用其载体，并在成年后无药物条件下评估工作记忆。虽然青春期自我施用 WIN 对短期空间记忆或成人工作记忆没有显着影响，但实验者施用 WIN 可以改善成人工作记忆表现，这在低剂量组中更为明显。因此，低剂量的青少年 WIN 暴露，无论是自我给药还是实验者给药，都会导致雌性大鼠成年工作记忆表现的改善或没有变化，与之前在雄性大鼠中发现的结果相似。
Marijuana is a prevalent illicit substance used by adolescents, and several studies have indicated that adolescent use can lead to long-term cognitive deficits including problems with attention and memory. However, preclinical animal studies that observe cognitive deficits after cannabinoid exposure during adolescence utilize experimenter administration of doses of cannabinoids that may exceed what an organism would choose to take, suggesting that contingency and dose are critical factors that need to be addressed in translational models of consequences of cannabinoid exposure. Indeed, we recently developed an adolescent cannabinoid self-administration paradigm in male rats, and found that prior adolescent self-administration of the cannabinoid receptor agonist WIN55,212-2 (WIN) resulted in improved working memory performance in adulthood. In addition, the doses self-administered were not as high as those that are found to produce memory deficits. However, given known sex differences in both drug self-administration and learning and memory processes, it is possible that cannabinoid self-administration could have different cognitive consequences in females. Therefore, we aimed to explore the effects of self-administered vs. experimenter-administered WIN in adolescent female rats on adult cognitive function. Female rats were trained to self-administer WIN daily throughout adolescence (postnatal day 34–59). A control group self-administered vehicle solution. The acute effects of adolescent WIN self-administration on memory were determined using a short-term spatial memory test 24 h after final SA session; and the long-term effects on cognitive performance were assessed during protracted abstinence in adulthood using a delayed-match-to-sample working memory task. In a separate experiment, females were given daily intraperitoneal (IP) injections of a low or high dose of WIN, corresponding to self-administered and typical experimenter-administered doses, respectively, or its vehicle during adolescence and working memory was assessed under drug-free conditions in adulthood. While self-administration of WIN in adolescence had no significant effects on short-term spatial memory or adult working memory, experimenter administration of WIN resulted in improved adult working memory performance that was more pronounced in the low dose group. Thus, low-dose adolescent WIN exposure, whether self-administered or experimenter-administered, results in either improvements or no change in adult working memory performance in female rats, similar to previous results found in males.
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影响因子：
5.3
作者：
Becker, Jill B.;Monteggia, Lisa M.;Bale, Tracy L.
通讯作者：
Bale, Tracy L.
DOI：
10.1016/j.pbb.2016.01.007
发表时间：
2017-01
期刊：
Pharmacology, biochemistry, and behavior
影响因子：
--
作者：
Fogel JS;Kelly TH;Westgate PM;Lile JA
通讯作者：
Lile JA
DOI：
10.1080/13803395.2014.893996
发表时间：
2014
影响因子：
2.2
作者：
Becker MP;Collins PF;Luciana M
通讯作者：
Luciana M
影响因子：
6.6
作者：
Marconi, Arianna;Di Forti, Marta;Vassos, Evangelos
通讯作者：
Vassos, Evangelos
影响因子：
3.4
作者：
Fuchs, RA;Tran-Nguyen, LTL;Neisewander, JL
通讯作者：
Neisewander, JL