Recent evidence implicates endogenous pituitary adenylyl cyclase activating polypeptide (PACAP) in the aversive effect of nicotine. In the present study, we assessed if nicotine‐induced conditioned place preference (CPP) or affective signs of nicotine withdrawal would be altered in the absence of PACAP and if there were any sex‐related differences in these responses. Male and female mice lacking PACAP and their wild‐type controls were tested for baseline place preference on day 1, received conditioning with saline or nicotine (1 mg/kg) on alternate days for 6 days and were then tested for CPP the next day. Mice were then exposed to four additional conditioning and were tested again for nicotine‐induced CPP 24 hr later. Controls were conditioned with saline in both chambers and tested similarly. All mice were then, 96 hr later, challenged with mecamylamine (3 mg/kg), and tested for anxiety‐like behaviors 30 min later. Mice were then, 2 hr later, forced to swim for 15 min and then tested for depression‐like behaviors 24 hr later. Our results showed that male but not female mice lacking PACAP expressed a significant CPP that was comparable to their wild‐type controls. In contrast, male but not female mice lacking PACAP exhibited reduced anxiety‐ and depression‐like behaviors compared to their wild‐type controls following the mecamylamine challenge. These results suggest that endogenous PACAP is involved in affective signs of nicotine withdrawal, but there is a sex‐related difference in this response.

中文翻译：

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垂体腺苷酸环化酶激活多肽在尼古丁戒断情绪症状中的作用。

最近的证据表明内源性垂体腺苷酸环化酶激活多肽 (PACAP) 与尼古丁的厌恶作用有关。在本研究中，我们评估了在没有 PACAP 的情况下，尼古丁诱导的条件性位置偏好 (CPP) 或尼古丁戒断的情感迹象是否会改变，以及这些反应是否存在任何性别相关差异。缺乏 PACAP 的雄性和雌性小鼠及其野生型对照在第 1 天接受基线位置偏好测试，隔天接受生理盐水或尼古丁 (1 mg/kg) 调理，持续 6 天，然后在第二天测试 CPP。然后让小鼠接受四次额外的调理，并在 24 小时后再次测试尼古丁诱导的 CPP。对照在两个室中都用盐水调节并进行类似测试。96 小时后，所有小鼠都 用美加明 (3 mg/kg) 挑战，并在 30 分钟后测试焦虑样行为。2 小时后，小鼠被迫游泳 15 分钟，然后在 24 小时后测试抑郁样行为。我们的结果表明，缺乏 PACAP 的雄性而非雌性小鼠表达了与其野生型对照相当的显着 CPP。相比之下，缺乏 PACAP 的雄性而非雌性小鼠在接受美加明攻击后与其野生型对照相比表现出减少的焦虑和抑郁样行为。这些结果表明内源性 PACAP 与尼古丁戒断的情感迹象有关，但这种反应存在性别相关的差异。被迫游泳 15 分钟，然后在 24 小时后测试抑郁样行为。我们的结果表明，缺乏 PACAP 的雄性而非雌性小鼠表达了与其野生型对照相当的显着 CPP。相比之下，缺乏 PACAP 的雄性而非雌性小鼠在接受美加明攻击后与其野生型对照相比表现出减少的焦虑和抑郁样行为。这些结果表明内源性 PACAP 与尼古丁戒断的情感迹象有关，但这种反应存在性别相关的差异。被迫游泳 15 分钟，然后在 24 小时后测试抑郁样行为。我们的结果表明，缺乏 PACAP 的雄性而非雌性小鼠表达了与其野生型对照相当的显着 CPP。相比之下，缺乏 PACAP 的雄性而非雌性小鼠在接受美加明攻击后与其野生型对照相比表现出减少的焦虑和抑郁样行为。这些结果表明内源性 PACAP 与尼古丁戒断的情感迹象有关，但这种反应存在性别相关的差异。在美加明攻击后，与野生型对照相比，缺乏 PACAP 的雄性而非雌性小鼠表现出减少的焦虑和抑郁样行为。这些结果表明内源性 PACAP 与尼古丁戒断的情感迹象有关，但这种反应存在性别相关的差异。在美加明攻击后，与野生型对照相比，缺乏 PACAP 的雄性而非雌性小鼠表现出更少的焦虑和抑郁样行为。这些结果表明内源性 PACAP 与尼古丁戒断的情感迹象有关，但这种反应存在性别相关的差异。