Evidence of Altered Brain Responses to Nicotine in an Animal Model of Attention Deficit/Hyperactivity Disorder.
Evidence of Altered Brain Responses to Nicotine in an Animal Model of Attention Deficit/Hyperactivity Disorder.
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注意力缺陷/多动症动物模型中大脑对尼古丁反应改变的证据。
DOI：
10.1093/ntr/ntx088
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
King,JeanA
中科院分区：
文献类型：
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作者：
Poirier,GuillaumeL;Huang,Wei;Tam,Kelly;DiFranza,JosephR;King,JeanA
患有注意力缺陷/多动障碍（ADHD）的人更容易出现更早和更严重的尼古丁成瘾。为了阐明尼古丁与多动症之间的关系，我们在多动症动物模型中研究了尼古丁对功能性脑网络的影响。方法采用wake磁共振成像技术比较青春期（出生后44±2天）雄性自发性高血压大鼠（SHR）与Wistar-Kyoto和Sprague-Dawley两种对照大鼠（n= 16）的功能连系。我们分析了naïve动物在尼古丁暴露（0.4 mg/kg碱）前后的功能连通性，使用兴趣区域方法，重点关注先前涉及奖励和成瘾的16个区域。结果与对照组相比，SHR毒株对尼古丁的反应显示出腹侧被盖区（VTA）和脾后皮质之间的功能连接增加，表明对尼古丁的反应异常。相比之下，注射尼古丁后，在SHR中注射生理盐水后增加的vta -黑质连通性没有增加，这表明尼古丁使该回路的功能正常化。结论在SHR中，尼古丁在一个VTA回路中引发非典型反应，而在另一个回路中使其活动正常化。VTA与毒品奖励有广泛的关系。我们的数据表明，ADHD患者对尼古丁成瘾的易感性增加可能与VTA回路对尼古丁的反应改变有关。尼古丁成瘾在ADHD患者中更为常见。我们发现，与两个对照品系相比，在模拟ADHD的动物中，涉及VTA的两个回路对尼古丁的反应不同。在一个回路中，尼古丁使多动症动物的异常活动正常化，而在另一个回路中，尼古丁使多动症动物的非典型大脑反应正常化。VTA与毒品奖励有关。我们的结果将与尼古丁可能使ADHD患者异常的大脑活动正常化的解释相一致，并且尼古丁可能对ADHD患者更有益。
IntroductionIndividuals with attention deficit/hyperactivity disorder (ADHD) are susceptible to earlier and more severe nicotine addiction. To shed light on the relationship between nicotine and ADHD, we examined nicotine’s effects on functional brain networks in an animal model of ADHD.MethodsAwake magnetic resonance imaging was used to compare functional connectivity in adolescent (post-natal day 44 ± 2) males of the spontaneously hypertensive rat (SHR) strain and two control strains, Wistar-Kyoto and Sprague-Dawley (n= 16 each). We analyzed functional connectivity immediately before and after nicotine exposure (0.4 mg/kg base) in naïve animals, using a region-of-interest approach focussing on 16 regions previously implicated in reward and addiction.ResultsRelative to the control groups, the SHR strain demonstrated increased functional connectivity between the ventral tegmental area (VTA) and retrosplenial cortex in response to nicotine, suggesting an aberrant response to nicotine. In contrast, increased VTA-substantia nigra connectivity in response to a saline injection in the SHR was absent following a nicotine injection, suggesting that nicotine normalized function in this circuit.ConclusionsIn the SHR, nicotine triggered an atypical response in one VTA circuit while normalizing activity in another. The VTA has been widely implicated in drug reward. Our data suggest that increased susceptibility to nicotine addiction in individuals with ADHD may involve altered responses to nicotine involving VTA circuits.ImplicationsNicotine addiction is more common among individuals with ADHD. We found that two circuits involving the VTA responded differently to nicotine in animals that model ADHD in comparison to two control strains. In one circuit, nicotine normalized activity that was abnormal in the ADHD animals, while in the other circuit nicotine caused an atypical brain response in the ADHD animals. The VTA has been implicated in drug reward. Our results would be consistent with an interpretation that nicotine may normalize abnormal brain activity in ADHD, and that nicotine may be more rewarding for individuals with ADHD.