Extended access to nicotine leads to a CRF1 receptor dependent increase in anxiety-like behavior and hyperalgesia in rats.
Extended access to nicotine leads to a CRF1 receptor dependent increase in anxiety-like behavior and hyperalgesia in rats.
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DOI：
10.1111/adb.12077
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发表时间：
2015-01
影响因子：
3.4
通讯作者：
George O
中科院分区：
文献类型：
--
作者：
Cohen A;Treweek J;Edwards S;Leão RM;Schulteis G;Koob GF;George O
烟草依赖与戒烟过程中出现的负面情绪状态有关，包括焦虑和伤害性超敏。然而，目前尼古丁依赖的动物模型主要集中在尼古丁急性强化效应的中介机制上，而未能将戒烟期间增加的焦虑和疼痛与过量的尼古丁自我给药联系起来。在这里，我们测试了一种假设，即促肾上腺皮质激素释放因子-1(CRF1)受体的激活以及尼古丁戒断的情感和激励效应的出现只发生在长期(21小时/天，LGA)和不短(1小时/天，SHA)获得尼古丁自我给药的大鼠。在禁食3天后，对SHA和LGA大鼠进行焦虑样行为、伤害性阈值、躯体戒断迹象和尼古丁摄入量的测试。通过在杏仁中央核(CEA)全身或脑内注射CRF1受体拮抗剂MPZP来检测CRF1受体在戒断过程中的作用。LGA而不是SHA大鼠在戒断后表现出焦虑样行为和伤害性超敏反应的增加，这两种行为都预示着随后过量的尼古丁摄入，并通过全身应用MPZP来防止。CEA内注射MPZP可防止戒酒引起的尼古丁摄入量增加和伤害性超敏反应。这些发现表明，短时间获得尼古丁自我给药模型对烟草依赖的有效性有限，突出了延长间歇获得尼古丁自我给药模型与烟草依赖的翻译相关性，并表明CRF1受体的激活是戒断诱导的焦虑样行为、痛觉过敏和尼古丁过量摄入所必需的。
Tobacco dependence is associated with the emergence of negative emotional states during withdrawal, including anxiety and nociceptive hypersensitivity. However, the current animal models of nicotine dependence have focused on the mechanisms that mediate the acute reinforcing effects of nicotine and failed to link increased anxiety and pain during abstinence with excessive nicotine self-administration. Here, we tested the hypothesis that the activation of corticotropin-releasing factor-1 (CRF1) receptors and emergence of the affective and motivational effects of nicotine abstinence only occur in rats with long access (> 21 h/day, LgA) and not short (1 h/day, ShA) access to nicotine self-administration. ShA and LgA rats were tested for anxiety-like behavior, nociceptive thresholds, somatic signs of withdrawal, and nicotine intake after 3 days of abstinence. The role of CRF1 receptors during abstinence was tested using systemic or intracerebral infusion of MPZP, a CRF1 receptor antagonist, in the central nucleus of the amygdala (CeA). LgA but not ShA rats exhibited abstinence-induced increases in anxiety-like behavior and nociceptive hypersensitivity, which both predicted subsequent excessive nicotine intake and were prevented by systemic administration of MPZP. Intra-CeA MPZP infusion prevented abstinence-induced increases in nicotine intake and nociceptive hypersensitivity. These findings demonstrate that the model of short access to nicotine self-administration has limited validity for tobacco dependence, highlight the translational relevance of the model of extended-intermittent access to nicotine self-administration for tobacco dependence, and demonstrate that activation of CRF1 receptors is required for the emergence of abstinence-induced anxiety-like behavior, hyperalgesia, and excessive nicotine intake.
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影响因子：
3.3
作者：
Ji, Guangchen;Fu, Yu;Ruppert, Katherine A.;Neugebauer, Volker
通讯作者：
Neugebauer, Volker
DOI：
10.1073/pnas.0707585104
发表时间：
2007-10-23
影响因子：
11.1
作者：
George, Olivier;Ghozland, Sandy;Koob, George F.
通讯作者：
Koob, George F.
影响因子：
3.4
作者：
Basso, AM;Spina, M;Koob, GF
通讯作者：
Koob, GF
影响因子：
3.4
作者：
Irvine, EE;Bagnalasta, M;Chiamulera, C
通讯作者：
Chiamulera, C
影响因子：
8
作者：
Doubeni CA;Reed G;Difranza JR
通讯作者：
Difranza JR