Fu Yu, Pollandt Sebastian, Liu Jie, Krishnan Balaji, Genzer Kathy, Orozco-Cabal Luis, Gallagher Joel P, Shinnick-Gallagher Patricia
Department of Pharmacology and Toxicology, Medical Branch, University of Texas, 301 University Blvd., Galveston, TX 77555-1031, USA.
J Neurophysiol. 2007 Jan;97(1):937-41. doi: 10.1152/jn.00349.2006. Epub 2006 Nov 1.
The amygdala is part of the brain reward circuitry that plays a role in cocaine-seeking and abstinence in animals and cocaine craving and relapse in humans. Cocaine-seeking is elicited by cocaine-associated cues, and the basolateral amygdala (BLA) and CeA are essential in forming and communicating drug-related associations that are thought to be critical in long-lasting relapse risk associated with drug addiction. Here we simulated a cue stimulus with high-frequency stimulation (HFS) of the BLA-CeA pathway to examine mechanisms that may contribute to drug-related associations. We found enhanced long-term potentiation (LTP) after 14-day but not 1-day withdrawal from 7-day cocaine treatment mediated through N-methyl-d-aspartate (NMDA) receptors (NRs), L-type voltage-gated calcium channels (L-VGCCs), and corticotropin-releasing factor (CRF)(1) receptors; this was accompanied by increased phosphorylated NR1 and CRF(1) protein not associated with changes in NMDA/AMPA ratios in amygdalae from cocaine-treated animals. We suggest that these signaling mechanisms may provide therapeutic targets for the treatment of cocaine cravings.
杏仁核是大脑奖赏回路的一部分，在动物的觅可卡因行为和戒断过程中发挥作用，在人类的可卡因渴望和复发过程中也起作用。与可卡因相关的线索会引发觅可卡因行为，基底外侧杏仁核（BLA）和中央杏仁核（CeA）对于形成和传递与药物相关的关联至关重要，而这些关联被认为在与药物成瘾相关的长期复发风险中起着关键作用。在此，我们通过对BLA-CeA通路进行高频刺激（HFS）来模拟线索刺激，以研究可能促成与药物相关关联的机制。我们发现，在从7天的可卡因治疗中戒断14天而非1天后，通过N-甲基-D-天冬氨酸（NMDA）受体（NRs）、L型电压门控钙通道（L-VGCCs）和促肾上腺皮质激素释放因子（CRF）（1）受体介导，长期增强（LTP）得到增强；这伴随着磷酸化NR1和CRF（1）蛋白增加，且这与可卡因处理动物杏仁核中NMDA/AMPA比值的变化无关。我们认为，这些信号传导机制可能为治疗可卡因渴望提供治疗靶点。
