阻断杏仁中央核内的促肾上腺皮质释放因子受体 1 可预防下丘脑后侧室旁核内给予食欲素-A 诱导的雄性大鼠可卡因觅药行为。
Blockade of corticotropin-releasing factor receptor 1 in the central amygdala prevents cocaine-seeking behaviour induced by orexin-A administered to the posterior paraventricular nucleus of the thalamus in male rats.
机构信息
From The Scripps Research Institute, La Jolla, California, USA (Matzeu, Martin-Fardon).
出版信息
J Psychiatry Neurosci. 2021 Jul 28;46(4):E459-E471. doi: 10.1503/jpn.200213.
BACKGROUND
Orexin-A (OrxA) administration in the posterior paraventricular nucleus of the thalamus (pPVT) reinstates extinguished cocaine-seeking behaviour following extended access to the drug (a model of dependence). The pPVT receives and integrates information associated with emotionally salient events and sends excitatory inputs to brain regions involved in the expression of emotional states, such as those driving cocaine-seeking behaviour (i.e., the nucleus accumbens, the central nucleus of the amygdala [CeA], the basolateral amygdala, the bed nucleus of the stria terminalis [BNST] and the prefrontal cortex).
METHODS
We monitored the activation pattern of these regions (measured by Fos) during cocaine-seeking induced by OrxA administered to the pPVT. The BNST and CeA emerged as being selectively activated. To test whether the functionality of these regions was pivotal during OrxA-induced cocaine-seeking behaviour, we transiently inactivated these regions concomitantly with OrxA administration to the pPVT. We then tested the participation of corticotropin-releasing factor receptors (CRF1) in the CeA during OrxA-induced cocaine-seeking using the CRF1 antagonist CP154526.
RESULTS
We observed selective activation of the CeA and BNST during cocaine-seeking induced by OrxA administered to the pPVT, but only transient inactivation of the CeA prevented cocaine-seeking behaviour. Administration of CP154526 to the CeA prevented OrxAinduced cocaine-seeking behaviour.
LIMITATIONS
The use of only male rats could have been a limitation. Other limitations could have been the use of an indirect approach to test the hypothesis that administration of OrxA to the pPVT drives cocaine-seeking via CRF1 signalling in the CeA, and a lack of analysis of the participation of CeA subregions.
CONCLUSION
Cocaine-seeking behaviour induced by OrxA administered to the pPVT is driven by activation of the CeA via CRF1 signalling.
背景
在后丘脑室旁核（pPVT）给予食欲素-A（OrxA）可恢复延长可卡因接触后可卡因寻求行为（依赖模型）。pPVT 接收和整合与情绪相关的事件的信息，并向涉及表达情绪状态的脑区发送兴奋性输入，例如驱动可卡因寻求行为的脑区（即伏隔核、杏仁核中央核[CeA]、基底外侧杏仁核、终纹床核[BNST]和前额叶皮质）。
方法
我们监测了这些区域（通过 Fos 测量）在 pPVT 给予 OrxA 诱导的可卡因寻求期间的激活模式。BNST 和 CeA 被选择性激活。为了测试这些区域在 OrxA 诱导的可卡因寻求行为中的功能是否至关重要，我们在 pPVT 给予 OrxA 的同时暂时失活这些区域。然后，我们使用 CRF1 拮抗剂 CP154526 测试了 CeA 中 CRF1 受体（CRF1）在 OrxA 诱导的可卡因寻求中的参与。
结果
我们观察到在 pPVT 给予 OrxA 诱导的可卡因寻求期间，CeA 和 BNST 选择性激活，但仅短暂失活 CeA 可预防可卡因寻求行为。CP154526 给药到 CeA 可预防 OrxA 诱导的可卡因寻求行为。
局限性
仅使用雄性大鼠可能是一个限制。其他限制可能是使用间接方法来测试以下假设，即 pPVT 给予 OrxA 通过 CeA 中的 CRF1 信号驱动可卡因寻求，以及缺乏对 CeA 亚区参与的分析。
结论
pPVT 给予 OrxA 诱导的可卡因寻求行为是由 CeA 中 CRF1 信号驱动的。
Zotero 插件