CRF antagonism within the ventral tegmental area but not the extended amygdala attenuates the anxiogenic effects of cocaine in rats.
CRF antagonism within the ventral tegmental area but not the extended amygdala attenuates the anxiogenic effects of cocaine in rats.
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DOI：
10.1016/j.pbb.2015.10.002
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发表时间：
2015-11
期刊：
影响因子：
--
通讯作者：
Wenzel JM
中科院分区：
文献类型：
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作者：
Ettenberg A;Cotten SW;Brito MA;Klein AK;Ohana TA;Margolin B;Wei A;Wenzel JM
除了最初的奖励作用外，可卡因已被证明产生深刻的负面/焦虑作用。最近关于可卡因的焦虑作用的研究已经检查了促肾上腺皮质激素释放因子（CRF）的作用，特别关注驻留在延伸杏仁核（即杏仁核的中央核[CeA]和终纹的床核[BNST]）的CRF细胞体以及该区域内的相互连接和区域外的投射（例如，腹侧被盖区（VTA）。在本研究中，通过BNST内、CeA内或VTA内应用CRF拮抗剂D-Phe CRF（12-41）或astressin-B产生局部CRF受体拮抗作用。在静脉注射可卡因自我给药的跑道模型中检查了这些治疗的效果，该模型已被证明对同一试验中同一动物中药物的初始奖励和延迟焦虑作用敏感。可卡因的这些双重作用反映在关于目标框条目的接近-回避冲突（“撤退行为”）的发展中，该冲突源于受试者对目标形成的混合关联。VTA内的CRF拮抗作用，而不是CeA或BNST，显着降低了接近-回避撤退行为的频率，而不受影响的开始潜伏期（可卡因的正向激励特性的指数）。这些结果表明，关键CRF受体与急性可卡因给药相关的焦虑状态可能位于扩展杏仁核之外，并可能涉及CRF投射到腹侧被盖区。
In addition to its initial rewarding effects, cocaine has been shown to produce profound negative/anxiogenic actions. Recent work on the anxiogenic effects of cocaine has examined the role of corticotropin releasing factor (CRF), with particular attention paid to the CRF cell bodies resident to the extended amygdala (i.e, the central nucleus of the amygdala [CeA] and the bed nucleus of the stria terminalis [BNST]) and the interconnections within and projections outside the region (e.g., to the ventral tegmental area [VTA]). In the current study, localized CRF receptor antagonism was produced by intra-BNST, intra-CeA or intra-VTA application of the CRF antagonists, D-Phe CRF (12-41) or astressin-B. The effect of these treatments were examined in a runway model of i.v. cocaine self-administration that has been shown to be sensitive to both the initial rewarding and delayed anxiogenic effects of the drug in the same animal on the same trial. These dual actions of cocaine are reflected in the development of an approach-avoidance conflict (“retreat behaviors”) about goal box entry that stems from the mixed associations that subjects form about the goal. CRF antagonism within the VTA, but not the CeA or BNST, significantly reduced the frequency of approach-avoidance retreat behaviors while leaving start latencies (an index of the positive incentive properties of cocaine) unaffected. These results suggest that the critical CRF receptors contributing to the anxiogenic state associated with acute cocaine administration may lie outside the extended amygdala, and likely involve CRF projections to the VTA.