Calcium/calmodulin-stimulated adenylyl cyclases 1 and 8 regulate reward-related brain activity and ethanol consumption.
Calcium/calmodulin-stimulated adenylyl cyclases 1 and 8 regulate reward-related brain activity and ethanol consumption.
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DOI：
10.1007/s11682-018-9856-6
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发表时间：
2019-04
影响因子：
3.2
通讯作者：
Conti AC
中科院分区：
文献类型：
--
作者：
Bosse KE;Ghoddoussi F;Eapen AT;Charlton JL;Susick LL;Desai K;Berkowitz BA;Perrine SA;Conti AC
有证据表明，奖励相关网络中基础活动的升高（例如，皮质-基底神经节-丘脑网络）和酗酒的脆弱性。钙通道功能和环磷酸腺苷（cAMP）/蛋白激酶A介导的信号传导是奖励神经回路和奖励相关行为的关键调节剂。钙/钙调素刺激的腺苷酸环化酶（AC）1和8对细胞内钙的活性依赖性增加敏感，并催化cAMP的产生。因此，我们假设AC 1和8调节皮质-基底节-丘脑回路的奖励区域的大脑活动，这种调节影响预测自愿饮酒反应。通过锰增强磁共振成像和慢性间歇性乙醇接入程序评估了这一假设。与野生型对照组（WT，C57 BL/6小鼠）相比，AC 1和AC 8基因缺失的乙醇未处理小鼠（DKO小鼠）表现出与奖赏处理相关的皮质-基底节-丘脑区域内基线活动的双侧降低。在皮质-基底神经节-丘脑网络之外的区域或与奖赏处理无关的网络内的区域，显著的活动变化并不明显。平行研究表明，与WT小鼠相比，DKO小鼠中的奖励网络功能减退预测了对乙醇浓度升高（12%，20%和30%）的消费和偏好水平的显着减弱，这种效果在延长20%乙醇的使用时间（14次）后仍保持不变。总之，这些数据支持AC 1和8在皮质-基底神经节-丘脑活动中的贡献，以及这种对饮酒行为的调节影响的预测价值，这值得将来评估钙刺激的AC在神经过程中对适应不良饮酒的脆弱性。本文的在线版本（10.1007/s11682-018-9856-6）包含补充材料，可供授权用户使用。
Evidence suggests a predictive link between elevated basal activity within reward-related networks (e.g., cortico-basal ganglia-thalamic networks) and vulnerability for alcoholism. Both calcium channel function and cyclic adenosine monophosphate (cAMP)/protein kinase A-mediated signaling are critical modulators of reward neurocircuitry and reward-related behaviors. Calcium/calmodulin-stimulated adenylyl cyclases (AC) 1 and 8 are sensitive to activity-dependent increases in intracellular calcium and catalyze cAMP production. Therefore, we hypothesized AC1 and 8 regulate brain activity in reward regions of the cortico-basal ganglia-thalamic circuit and that this regulatory influence predicts voluntary ethanol drinking responses. This hypothesis was evaluated by manganese-enhanced magnetic resonance imaging and chronic, intermittent ethanol access procedures. Ethanol-naïve mice with genetic deletion of both AC1 and 8 (DKO mice) exhibited bilateral reductions in baseline activity within cortico-basal ganglia-thalamic regions associated with reward processing compared to wild-type controls (WT, C57BL/6 mice). Significant activity changes were not evident in regions either outside of the cortico-basal ganglia-thalamic network or within the network that are not associated with reward processing. Parallel studies demonstrated that reward network hypoactivity in DKO mice predicted a significant attenuation in consumption and preference levels to escalating ethanol concentrations (12, 20 and 30%) compared to WT mice, an effect that was maintained over extended access (14 sessions) to 20% ethanol. Summarizing, these data support a contribution of AC1 and 8 in cortico-basal ganglia-thalamic activity and the predictive value of this regulatory influence on ethanol drinking behavior, which merits the future evaluation of calcium-stimulated ACs in the neural processes that engender vulnerability to maladaptive alcohol drinking. The online version of this article (10.1007/s11682-018-9856-6) contains supplementary material, which is available to authorized users.
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影响因子：
8.8
作者：
Dittmer PJ;Dell'Acqua ML;Sather WA
通讯作者：
Sather WA
使用锰增强的磁共振成像（MEMRI）的αCAMKII杂合敲除小鼠中细胞活性的体内评估。
影响因子：
3.5
作者：
Hattori S;Hagihara H;Ohira K;Aoki I;Saga T;Suhara T;Higuchi M;Miyakawa T
通讯作者：
Miyakawa T
影响因子：
5.7
作者：
Gozzi A;Agosta F;Massi M;Ciccocioppo R;Bifone A
通讯作者：
Bifone A
影响因子：
2.9
作者：
Bachtell, RK;Wang, YM;Ryabinin, AE
通讯作者：
Ryabinin, AE
影响因子：
1.3
作者：
Duncan, Susan C;Strycker, Lisa A;Duncan, Terry E
通讯作者：
Duncan, Terry E