Age-dependent regulation of GABA transmission by kappa opioid receptors in the basolateral amygdala of Sprague-Dawley rats.
Age-dependent regulation of GABA transmission by kappa opioid receptors in the basolateral amygdala of Sprague-Dawley rats.
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DOI：
10.1016/j.neuropharm.2017.01.036
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发表时间：
2017-05-01
影响因子：
4.7
通讯作者：
Diaz MR
中科院分区：
文献类型：
--
作者：
Przybysz KR;Werner DF;Diaz MR
焦虑症是世界上最常见和最令人衰弱的精神疾病之一。越来越多的证据表明，从青春期到成年期，焦虑症的发病率呈年龄依赖性上升，提示潜在的神经发育机制。已知κ阿片受体（KOR）有助于焦虑的发展和表达;然而，KOR在基底外侧杏仁核（BLA）中的功能作用是未知的，基底外侧杏仁核是介导焦虑的关键大脑结构，特别是在个体发育中。在青少年（出生后30-45天（P））和成年（P60+）雄性Sprague-Dawley大鼠的急性脑切片中使用全细胞膜片钳电生理学，我们发现KOR激活增加了青少年BLA中GABA介导的自发抑制性突触后电流（sIPSC）的频率，而对成年BLA或sIPSC振幅没有影响。KOR效应被KOR拮抗剂nor-BNI阻断，单独使用它在任何年龄都不会改变GABA的传递，KOR激动剂的效应是TTX敏感的。此外，KOR激活并没有改变BLA在任何年龄段的多巴胺能传递。相比之下，U69593在两个年龄段抑制中央杏仁核（CeA）中的sIPSC频率，而不改变sIPSC振幅。蛋白质印迹分析KOR的表达表明，KOR水平是没有不同的两个年龄之间的BLA或CeA。这是第一项研究提供了令人信服的证据，证明在参与启动和介导焦虑的主要大脑区域之一中存在一种新颖独特的神经调节开关，这可能有助于焦虑症的个体发生性上升。
Anxiety disorders are one of the most common and debilitating mental illnesses worldwide. Growing evidence indicates an age-dependent rise in the incidence of anxiety disorders from adolescence through adulthood, suggestive of underlying neurodevelopmental mechanisms. Kappa opioid receptors (KORs) are known to contribute to the development and expression of anxiety; however, the functional role of KORs in the basolateral amygdala (BLA), a brain structure critical in mediating anxiety, particularly across ontogeny, are unknown. Using whole-cell patch-clamp electrophysiology in acute brain slices from adolescent (postnatal day (P) 30–45) and adult (P60+) male Sprague-Dawley rats, we found that KOR activation increased the frequency of GABAA-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in the adolescent BLA, without an effect in the adult BLA or on sIPSC amplitude at either age. The KOR effect was blocked by the KOR antagonist, nor-BNI, which alone did not alter GABA transmission at either age, and the effect of the KOR agonist was TTX-sensitive. Additionally, KOR activation did not alter glutamatergic transmission in the BLA at either age. In contrast, U69593 inhibited sIPSC frequency in the central amygdala (CeA) at both ages, without altering sIPSC amplitude. Western blot analysis of KOR expression indicated that KOR levels were not different between the two ages in either the BLA or CeA. This is the first study to provide compelling evidence for a novel and unique neuromodulatory switch in one of the primary brain regions involved in initiating and mediating anxiety that may contribute to the ontogenic rise in anxiety disorders.