Intermittent nicotine exposure upregulates nAChRs in VTA dopamine neurons and sensitises locomotor responding to the drug.
Intermittent nicotine exposure upregulates nAChRs in VTA dopamine neurons and sensitises locomotor responding to the drug.
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DOI：
10.1111/ejn.12114
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发表时间：
2013-03
期刊：
影响因子：
--
通讯作者：
Vezina P
中科院分区：
文献类型：
--
作者：
Baker LK;Mao D;Chi H;Govind AP;Vallejo YF;Iacoviello M;Herrera S;Cortright JJ;Green WN;McGehee DS;Vezina P
从腹侧被盖区(VTA)到伏核(NAcc)的多巴胺能投射介导了包括尼古丁在内的许多滥用药物的行为和动机效应。重复间歇给药，通常与最初的药物暴露有关，使这一途径中的多巴胺(DA)神经元的反应性变得敏感，增强药物释放的运动行为，促进药物的追逐和自我给药。在这里，我们发现，在尼古丁诱导运动敏化的过程中，激活VTA中的烟碱型乙酰胆碱受体(NAChRs)，而不是NAcc中的烟碱型乙酰胆碱受体(NAChRs)是必不可少的。反复间歇尼古丁暴露(4×0.4 mg/kg，基础，ip，超过7天)是一种导致持久运动敏化的方案，在最后一次暴露注射后的几个小时内，也引起VTA中nAChRs的上调，但NAcc中的nAChRs没有上调。在VTA的DA神经元中，选择性地观察到功能性nAChR的上调，而在GABA神经元中则未观察到。紧随其后的是对这些细胞的兴奋性输入的长期增强和NAcc中尼古丁诱发的DA溢出的增加。在这种暴露方案下，没有观察到戒断症状。因此，尼古丁对VTA内DA神经元nAChRs的间歇性激活和上调可能有助于行为敏感化的发展和尼古丁成瘾的增加。
Dopaminergic projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAcc) mediate the behavioral and motivational effects of many drugs of abuse, including nicotine. Repeated intermittent administration of these drugs, a pattern often associated with initial drug exposure, sensitizes the reactivity of dopamine (DA) neurons in this pathway, enhances the locomotor behaviors the drugs emit, and promotes their pursuit and self-administration. Here we show that activation of nicotinic acetylcholine receptors (nAChRs) in the VTA, but not the NAcc, is essential for the induction of locomotor sensitization by nicotine. Repeated intermittent nicotine exposure (4 × 0.4 mg/kg, base, i.p., administered over 7 days), a regimen leading to long-lasting locomotor sensitization, also produced upregulation of nAChRs in the VTA, but not the NAcc, in the hours following the last exposure injection. Functional nAChR upregulation was observed selectively in DA but not GABA neurons in the VTA. These effects were followed by long-term potentiation of excitatory inputs to these cells and increased nicotine-evoked DA overflow in the NAcc. Withdrawal symptoms were not observed following this exposure regimen. Thus, intermittent activation and upregulation by nicotine of nAChRs in DA neurons in the VTA may contribute to the development of behavioral sensitization and increased liability for nicotine addiction.
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影响因子：
16.2
作者：
Mansvelder, HD;McGehee, DS
通讯作者：
McGehee, DS
影响因子：
5.3
作者：
Gotti, Cecilia;Guiducci, Stefania;Zoli, Michele
通讯作者：
Zoli, Michele
影响因子：
3.4
作者：
Ferrari, R;Le Novère, N;Zoli, M
通讯作者：
Zoli, M
影响因子：
7.3
作者：
CLARKE, PBS;KUMAR, R
通讯作者：
KUMAR, R
影响因子：
3.8
作者：
COLLINS, AC;ROMM, E;WEHNER, JM
通讯作者：
WEHNER, JM