Sex differences in cocaine conditioned place preference in C57BL/6J mice.

Sex differences in cocaine conditioned place preference in C57BL/6J mice.
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DOI:
10.1097/wnr.0000000000000053
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发表时间:
2014-01-22
期刊:
影响因子:
1.7
通讯作者:
Lasek AW
Lasek AW
中科院分区:
医学4区
文献类型:
--
作者:
Hilderbrand ER;Lasek AW

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男性和女性对可卡因和可卡因相关线索的主观影响的反应不同,这对可卡因成瘾的发展和维持有影响。在大鼠身上进行的临床前研究模拟了可卡因成瘾的各个方面,在很大程度上证实了这些结果,表明雌性大鼠可能对可卡因的有益特性更敏感。导致可卡因奖赏性别差异的分子机制在很大程度上还没有确定,尽管性激素被认为起到了作用。小鼠通常被用作研究影响各种精神障碍的分子和遗传因素的模式生物。特别是,近亲交配的C57BL/6小鼠品系经常被用于与药物滥用有关的行为研究。为了开始了解可能影响可卡因奖赏的激素、分子和遗传机制,我们直接比较了雄性和雌性C57BL/6J小鼠在可卡因条件性位置偏好(CPP)中的表现,CPP是一种测试滥用药物的奖赏和线索相关属性的测试。我们让小鼠服用三种剂量的可卡因,并检测偏爱和偏爱的消退。我们发现,可卡因CPP的获得在雄性和雌性小鼠之间没有差异。然而,与雌性小鼠相比,在最低剂量的可卡因作用下,雄性小鼠的可卡因CPP消退时间延迟。我们的结论是,在极低剂量的可卡因作用下,C57BL/6J小鼠的可卡因CPP存在性别差异。
Men and women respond differently to the subjective effects of cocaine and cocaine-associated cues, which has implications for the development and maintenance of cocaine addiction. Preclinical studies performed in rats, modeling various aspects of cocaine addiction, have largely validated these results, indicating that female rats may be more sensitive to the rewarding properties of cocaine. The molecular mechanisms leading to sex differences in cocaine reward have largely not been determined, although sex hormones are thought to play a role. The mouse is commonly used as a model organism to study the molecular and genetic factors that influence a variety of psychiatric disorders. In particular, the inbred C57BL/6 mouse strain is often used for behavioral studies related to substance abuse. To begin to understand the hormonal, molecular and genetic mechanisms that might affect cocaine reward, we directly compared male and female C57BL/6J mice in cocaine conditioned place preference (CPP), a test that examines the rewarding and cue-associated properties of drugs of abuse. We conditioned mice at three doses of cocaine and examined preference and extinction of preference. We found that the acquisition of cocaine CPP did not differ between male and female mice. However, extinction of cocaine CPP was delayed in male mice compared to females at the lowest dose of cocaine. We conclude that sex differences in cocaine CPP can be observed in C57BL/6J mice at very low doses of cocaine.