Extended access nicotine self-administration with periodic deprivation increases immature neurons in the hippocampus.
Extended access nicotine self-administration with periodic deprivation increases immature neurons in the hippocampus.
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DOI：
10.1007/s00213-014-3685-0
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发表时间：
2015-01
影响因子：
3.4
通讯作者：
Mandyam, Chitra D.
中科院分区：
文献类型：
--
作者：
Cohen, Ami;Soleiman, Matthew T.;Talia, Reneta;Koob, George F.;George, Olivier;Mandyam, Chitra D.
有限的尼古丁自我给药途径减少了海马神经发生，为尼古丁对海马神经元可塑性的有害影响提供了一种机制。然而，最近的研究表明，有限的尼古丁自我给药并没有表现出尼古丁依赖的关键特征，如动机戒断和剥夺尼古丁后对尼古丁的动机增加。本研究采用长时间尼古丁自我给药（0.03 mg/kg/输注，21小时/天(d), 4d）和间歇性剥夺（3d），持续14周，以验证该模型与有限摄入（1小时/天，4d）相比增强尼古丁寻求并在海马神经发生中产生明显反应的假设。延长接触组的动物在最后一次剥夺之前或之后进行灌注，而限制接触组的动物在最后一次剥夺之后进行灌注。有限的尼古丁自我给药和长期的尼古丁自我给药并周期性剥夺对内侧前额叶皮层（mPFC）少突胶质细胞祖细胞的增殖和分化没有影响。相反，定期剥夺尼古丁的长期自我给药增强了海马神经祖细胞的增殖和分化。此外，在海马体中，在经历长期尼古丁自我给药的大鼠中，分化的neurod标记细胞的数量与增强的尼古丁寻求强烈正相关。这些发现表明，在成年期，尼古丁自我给药的时间延长与限制对新少突胶质细胞和新神经元的产生有不同的影响。长时间尼古丁自我给药大鼠分化细胞数量的增加可能导致海马神经发生异常，并可能导致依赖海马的不适应成瘾样行为。
Limited access nicotine self-administration decreases hippocampal neurogenesis, providing a mechanism for the deleterious effects of nicotine on hippocampal neuronal plasticity. However, recent studies have shown that limited access nicotine self-administration does not exhibit key features of nicotine dependence such as motivational withdrawal and increased motivation for nicotine after deprivation. The present study used extended access nicotine self-administration (0.03 mg/kg/infusion, 21h/day (d), 4d) with intermittent periods of deprivation (3d) for 14 weeks, to test the hypothesis that this model enhances nicotine seeking and produces distinct responses in hippocampal neurogenesis when compared with limited access (1h/day, 4d) intake. Animals in the extended access group were either perfused prior to or following their final deprivation period, whereas animals in the limited access group were perfused after their last session. Limited access nicotine self-administration and extended access nicotine self-administration with periodic deprivation did not affect proliferation and differentiation of oligodendrocyte progenitors in the medial prefrontal cortex (mPFC). Conversely, extended access nicotine self-administration with periodic deprivation enhanced proliferation and differentiation of hippocampal neural progenitors. Furthermore, in the hippocampus, the number of differentiating NeuroD-labeled cells strongly and positively correlated with enhanced nicotine seeking in rats that experienced extended access nicotine self-administration. These findings demonstrate that extended access versus limited access to nicotine self-administration differentially affects the generation of new oligodendroglia and new neurons during adulthood. The increases in the number of differentiating cells in extended access nicotine self-administering rats may consequently contribute to aberrant hippocampal neurogenesis and may contribute to maladaptive addiction-like behaviors dependent on the hippocampus.
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影响因子：
82.9
作者：
Eriksson, PS;Perfilieva, E;Gage, FH
通讯作者：
Gage, FH
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：
3.5
作者：
Becker, S
通讯作者：
Becker, S
影响因子：
3.4
作者：
CORRIGALL, WA;COEN, KM
通讯作者：
COEN, KM
影响因子：
3.4
作者：
Bora, Emre;Yuecel, Murat;Lubman, Dan I.
通讯作者：
Lubman, Dan I.