Adolescent cocaine exposure enhances goal-tracking behavior and impairs hippocampal cell genesis selectively in adult bred low-responder rats.
Adolescent cocaine exposure enhances goal-tracking behavior and impairs hippocampal cell genesis selectively in adult bred low-responder rats.
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DOI：
10.1007/s00213-017-4566-0
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发表时间：
2017-04
影响因子：
3.4
通讯作者：
Flagel SB
中科院分区：
文献类型：
--
作者：
García-Fuster MJ;Parsegian A;Watson SJ;Akil H;Flagel SB
青春期的环境挑战，如药物暴露，可能导致持久的行为和分子变化，导致终身适应不良的行为，包括成瘾。选择性繁殖的高反应（bHR）和低反应（bLR）大鼠代表了一种独特的模型，用于评估青少年环境操纵的长期影响，因为它们在许多成瘾相关的特征上存在固有的差异。bHR大鼠被认为是“成瘾倾向”，而bLR大鼠是“成瘾弹性”，至少在基线条件下。此外，相对于bLR，bHR大鼠更容易将激励动机价值归因于奖励线索或“符号跟踪”。我们利用bHR和bLR大鼠来确定青少年可卡因暴露是否可以改变其先天的行为和神经生物学特征，特别关注巴甫洛夫条件接近行为（即符号与目标跟踪）和海马神经发生。在青春期（出生后第33-39天），向bHR和bLR大鼠施用可卡因（15 mg/kg）或盐水7天，随后在成年期（PND 62-75）测试巴甫洛夫条件接近行为，其中照明杆（条件刺激）之后是食物颗粒（非条件刺激）的反应独立递送。针对杠杆和食物杯的行为分别记录为符号和目标跟踪。在PND 77通过免疫组织化学评价海马细胞发生。青少年可卡因暴露损害海马细胞的发生（增殖和生存），并增强了内在的倾向，目标跟踪在成年bLR，但不是bHR，大鼠。青少年可卡因暴露elevening刺激-奖励学习的持久变化和海马神经发生的持久缺陷选择性在成年bLR大鼠。
Environmental challenges during adolescence, such as drug exposure, can cause enduring behavioral and molecular changes that contribute to life-long maladaptive behaviors, including addiction. Selectively bred high-responder (bHR) and low-responder (bLR) rats represent a unique model for assessing the long-term impact of adolescent environmental manipulations, as they inherently differ on a number of addiction-related traits. bHR rats are considered “addiction-prone”, whereas bLR rats are “addiction-resilient”, at least under baseline conditions. Moreover, relative to bLRs, bHR rats are more likely to attribute incentive motivational value to reward cues, or to “sign-track”. We utilized bHR and bLR rats to determine whether adolescent cocaine exposure can alter their inborn behavioral and neurobiological profiles, with a specific focus on Pavlovian conditioned approach behavior (i.e. sign- vs. goal-tracking) and hippocampal neurogenesis. bHR and bLR rats were administered cocaine (15 mg/kg) or saline for 7 days during adolescence (postnatal day, PND 33–39) and subsequently tested for Pavlovian conditioned approach behavior in adulthood (PND 62–75), wherein an illuminated lever (conditioned stimulus) was followed by the response-independent delivery of a food pellet (unconditioned stimulus). Behaviors directed towards the lever and the food cup were recorded as sign- and goal-tracking, respectively. Hippocampal cell genesis was evaluated on PND 77 by immunohistochemistry. Adolescent cocaine exposure impaired hippocampal cell genesis (proliferation and survival) and enhanced the inherent propensity to goal-track in adult bLR, but not bHR, rats. Adolescent cocaine exposure elicits long-lasting changes in stimulus-reward learning and enduring deficits in hippocampal neurogenesis selectively in adult bLR rats.
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影响因子：
64.8
作者：
Flagel SB;Clark JJ;Robinson TE;Mayo L;Czuj A;Willuhn I;Akers CA;Clinton SM;Phillips PE;Akil H
通讯作者：
Akil H
影响因子：
10.6
作者：
Daws, Stephanie E.;Black, Yolanda D.;Naydenov, Alipi V.;Vassoler, Fair R.;Hanlin, Ryan P.;Konradi, Christine
通讯作者：
Konradi, Christine
影响因子：
5.3
作者：
Black, Yolanda D.;Maclaren, Fair R.;Konradi, Christine
通讯作者：
Konradi, Christine
影响因子：
4.7
作者：
Fitzpatrick CJ;Perrine SA;Ghoddoussi F;Galloway MP;Morrow JD
通讯作者：
Morrow JD
影响因子：
2.7
作者：
Flagel, Shelly B.;Watson, Stanley J.;Robinson, Terry E.
通讯作者：
Robinson, Terry E.