Suppression of cocaine relapse-like behaviors upon pimavanserin and lorcaserin co-administration.
Suppression of cocaine relapse-like behaviors upon pimavanserin and lorcaserin co-administration.
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DOI：
10.1016/j.neuropharm.2020.108009
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发表时间：
2020-05-15
影响因子：
4.7
通讯作者：
Cunningham KA
中科院分区：
文献类型：
--
作者：
Anastasio NC;Sholler DJ;Fox RG;Stutz SJ;Merritt CR;Bjork JM;Moeller FG;Cunningham KA
可卡因使用障碍（CUD）是一个主要的公共卫生挑战，美国食品和药物管理局（FDA）尚未批准药物治疗。CUD复发的倾向涉及几个脆弱性因素，包括对可卡因服用相关线索的敏感性。5-羟色胺（5-hydroxytryptamine，5-HT）神经传递，特别是通过5-HT 2A受体（5-HT 2AR）和5-HT 2C受体（5-HT 2CR），在临床前模型中与可卡因寻求性机制相关。在本实验中，我们在雄性大鼠中采用自我给药测定来研究FDA批准的选择性5-HT 2AR拮抗剂/反向激动剂匹莫范色林、选择性5-HT 2CR激动剂氯卡色林或其组合的急性和/或重复给药是否会改变可卡因摄入和/或可卡因寻求行为。我们发现，氯卡色林（而非匹莫范色林）急性给药可减少可卡因摄入，而匹莫范色林加氯卡色林不影响可卡因自我给药。相比之下，在可卡因自我给药的强制戒断期间重复给予匹莫范色林、氯卡色林或匹莫范色林+氯卡色林10天，可卡因寻求减弱，类似于每种配体的急性给药。综上所述，这些数据揭示了匹莫范色林加氯卡色林重复治疗减弱对CUD啮齿动物模型中复发样行为重要的因素的功效。这篇文章是题为“血清素研究：跨越尺度和界限”的特刊的一部分。
Cocaine use disorder (CUD) is a major public health challenge for which there are no pharmacotherapeutics approved by the United States Food and Drug Administration (FDA). The propensity to relapse in CUD involves several vulnerability factors including sensitivity to cues associated with cocaine-taking. Serotonin (5-hydroxytryptamine, 5-HT) neurotransmission, particularly through the 5-HT2A receptor (5-HT2AR) and 5-HT2C receptor (5-HT2CR), is mechanistically linked to cocaine-seeking in preclinical models. In the present experiments, we employed self-administration assays in male rats to investigate whether acute and/or repeated administration of the FDA-approved selective 5-HT2AR antagonist/inverse agonist pimavanserin, selective 5-HT2CR agonist lorcaserin or their combination would alter cocaine intake and/or cocaine-seeking behavior. We found that acute administration of lorcaserin, but not pimavanserin, attenuated cocaine intake while pimavanserin plus lorcaserin did not impact cocaine self-administration. In contrast, 10-days of repeated administration of pimavanserin, lorcaserin, or pimavanserin plus lorcaserin during forced abstinence from cocaine self-administration, blunted cocaine-seeking, similar to the acute administration of each ligand. Taken together, these data reveal the efficacy of repeated treatment with pimavanserin plus lorcaserin to attenuate factors important to relapse-like behaviors in rodent models of CUD. This article is part of the special issue entitled ‘Serotonin Research: Crossing Scales and Boundaries’.
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影响因子：
7.6
作者：
Banks, Matthew L.;Negus, S. Stevens
通讯作者：
Negus, S. Stevens
影响因子：
6.8
作者：
Anastasio, N. C.;Liu, S.;Moeller, F. G.
通讯作者：
Moeller, F. G.
DOI：
10.1124/jpet.116.236307
发表时间：
2016-12-01
影响因子：
3.5
作者：
Gerak, Lisa R.;Collins, Gregory T.;France, Charles P.
通讯作者：
France, Charles P.
影响因子：
7.6
作者：
Fletcher, Paul J.;Rizos, Zoe;Higgins, Guy A.
通讯作者：
Higgins, Guy A.
影响因子：
5
作者：
Cunningham, Kathryn A.;Anastasio, Noelle C.;Moeller, F. Gerard
通讯作者：
Moeller, F. Gerard