Adolescent cocaine self-administration induces habit behavior in adulthood: sex differences and structural consequences.
Adolescent cocaine self-administration induces habit behavior in adulthood: sex differences and structural consequences.
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DOI：
10.1038/tp.2016.150
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发表时间：
2016-08-30
影响因子：
6.8
通讯作者：
Gourley SL
中科院分区：
文献类型：
--
作者：
DePoy LM;Allen AG;Gourley SL
青少年使用可卡因增加了成年后滥用药物和成瘾的可能性，病因可能包括可卡因诱导的对所谓的“寻求回报”习惯的偏见。为了确定青春期接触可卡因是否确实影响成年后的决策策略，我们训练青春期小鼠自我口服可卡因。成年后，有自我管理升级史的男性对基于习惯的行为产生了偏见。相比之下，不断升级的女性并没有形成习惯偏见；相反，低应答率与后来的行为不灵活有关，与可卡因剂量无关。我们在报告的其余部分集中于了解青春期女性的个体差异如何预测长期行为结果。青春期低的、稳定的可卡因强化反应率与可卡因条件下的物体偏好和成年后内侧(初步)前额叶皮质树突棘头大小有关。同时，可卡因的弹性与眼眶额叶皮质深层的脊柱头部增大有关。成年后再次暴露在与可卡因相关的环境中，会激发“稳定反应者”的反应，然后GABAB激动剂巴氯芬和可能的酪氨酸受体激酶B(TrkB)激动剂7，8-二羟基黄酮会减少这种反应。总之，我们的发现突显了当摄入量增加时，女性相对于男性对可卡因诱导的习惯的适应能力。然而，青春期女性在工具性条件反射方面的失败可能会在成年后引发寻求奖励的行为，特别是在接触可卡因的情况下。
Adolescent cocaine use increases the likelihood of drug abuse and addiction in adulthood, and etiological factors may include a cocaine-induced bias towards so-called ‘reward-seeking' habits. To determine whether adolescent cocaine exposure indeed impacts decision-making strategies in adulthood, we trained adolescent mice to orally self-administer cocaine. In adulthood, males with a history of escalating self-administration developed a bias towards habit-based behaviors. In contrast, escalating females did not develop habit biases; rather, low response rates were associated with later behavioral inflexibility, independent of cocaine dose. We focused the rest of our report on understanding how individual differences in young-adolescent females predicted long-term behavioral outcomes. Low, ‘stable' cocaine-reinforced response rates during adolescence were associated with cocaine-conditioned object preference and enlarged dendritic spine head size in the medial (prelimbic) prefrontal cortex in adulthood. Meanwhile, cocaine resilience was associated with enlarged spine heads in deep-layer orbitofrontal cortex. Re-exposure to the cocaine-associated context in adulthood energized responding in ‘stable responders', which could then be reduced by the GABAB agonist baclofen and the putative tyrosine receptor kinase B (trkB) agonist, 7,8-dihydroxyflavone. Together, our findings highlight resilience to cocaine-induced habits in females relative to males when intake escalates. However, failures in instrumental conditioning in adolescent females may precipitate reward-seeking behaviors in adulthood, particularly in the context of cocaine exposure.
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影响因子：
5.6
作者：
DePoy LM;Perszyk RE;Zimmermann KS;Koleske AJ;Gourley SL
通讯作者：
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DOI：
10.1073/pnas.1208342109
发表时间：
2012-12-11
影响因子：
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作者：
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通讯作者：
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