Dysfunction of ventral tegmental area GABA neurons causes mania-like behavior.
Dysfunction of ventral tegmental area GABA neurons causes mania-like behavior.
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腹侧被盖区 GABA 神经元功能障碍导致躁狂样行为
DOI：
10.1038/s41380-020-0810-9
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发表时间：
2021-09
影响因子：
11
通讯作者：
Wisden W
中科院分区：
文献类型：
--
作者：
Yu X;Ba W;Zhao G;Ma Y;Harding EC;Yin L;Wang D;Li H;Zhang P;Shi Y;Yustos R;Vyssotski AL;Dong H;Franks NP;Wisden W
腹侧被盖区（VTA），多巴胺的重要来源，调节目标和奖励导向和社会行为，觉醒和睡眠。多巴胺神经元的过度激活会产生行为病理。但非多巴胺VTA神经元在精神疾病中的作用却很少被探索。损伤或化学抑制VTA gaba能（VTAVgat）神经元产生持续的觉醒，具有躁狂样特征：运动活动增加；对d -安非他明的敏感性增高；尾悬和强制游泳试验中静止时间减少；对蔗糖的偏好增加了。此外，睡眠剥夺后，vtavgatneuron受损的小鼠无法弥补失去的睡眠，即使它们是从睡眠剥夺的基线开始的，这表明睡眠稳态被忽略了。这种躁狂样的行为，包括睡眠不足，被丙戊酸酯逆转，并在治疗停止后重新出现。然而，锂盐和拉莫三嗪没有效果。低剂量地西泮部分减轻了运动过度，完全恢复了悬尾期间的静止时间。躁狂样行为主要依赖于多巴胺，因为D1/D2/D3受体拮抗剂减少了这些行为，但也部分依赖于vtavgatn向外侧下丘脑（LH）的投射。在悬挂尾巴和强制游泳试验中，在光学或化学上抑制LH中的vtavgatterminal可提高运动能力并减少静止时间。vtavgatneuron帮助设定动物（也许还有人类）的精神和身体活动水平。抑制vtavgat神经元的输入会增强清醒（活动增加，警觉性和动机增强），这对急性生存很有用。然而，在极端情况下，vtavgatneuron的抑制减少或失败会产生躁狂样症状（多动、快感、睡眠减少）。
The ventral tegmental area (VTA), an important source of dopamine, regulates goal- and reward-directed and social behaviors, wakefulness, and sleep. Hyperactivation of dopamine neurons generates behavioral pathologies. But any roles of non-dopamine VTA neurons in psychiatric illness have been little explored. Lesioning or chemogenetically inhibiting VTA GABAergic (VTAVgat) neurons generated persistent wakefulness with mania-like qualities: locomotor activity was increased; sensitivity to D-amphetamine was heightened; immobility times decreased on the tail suspension and forced swim tests; and sucrose preference increased. Furthermore, after sleep deprivation, mice with lesioned VTAVgatneurons did not catch up on lost sleep, even though they were starting from a sleep-deprived baseline, suggesting that sleep homeostasis was bypassed. The mania-like behaviors, including the sleep loss, were reversed by valproate, and re-emerged when treatment was stopped. Lithium salts and lamotrigine, however, had no effect. Low doses of diazepam partially reduced the hyperlocomotion and fully recovered the immobility time during tail suspension. The mania like-behaviors mostly depended on dopamine, because giving D1/D2/D3 receptor antagonists reduced these behaviors, but also partially on VTAVgatprojections to the lateral hypothalamus (LH). Optically or chemogenetically inhibiting VTAVgatterminals in the LH elevated locomotion and decreased immobility time during the tail suspension and forced swimming tests. VTAVgatneurons help set an animal’s (and perhaps human’s) mental and physical activity levels. Inputs inhibiting VTAVgatneurons intensify wakefulness (increased activity, enhanced alertness and motivation), qualities useful for acute survival. In the extreme, however, decreased or failed inhibition from VTAVgatneurons produces mania-like qualities (hyperactivity, hedonia, decreased sleep).
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影响因子：
4.6
作者：
Garzón-Niño J;Rodríguez-Muñoz M;Cortés-Montero E;Sánchez-Blázquez P
通讯作者：
Sánchez-Blázquez P
影响因子：
12.8
作者：
Lee Y;Zhang Y;Kim S;Han K
通讯作者：
Han K
影响因子：
3.3
作者：
Logan RW;McClung CA
通讯作者：
McClung CA
影响因子：
5.7
作者：
Greene RW;Bjorness TE;Suzuki A
通讯作者：
Suzuki A
影响因子：
25
作者：
Eban-Rothschild A;Rothschild G;Giardino WJ;Jones JR;de Lecea L
通讯作者：
de Lecea L