Wills Kiri L, DeVuono Marieka V, Limebeer Cheryl L, Vemuri Kiran, Makriyannis Alexandros, Parker Linda A
Department of Psychology, University of Guelph.
Center for Drug Discovery, Northeastern University.
Behav Neurosci. 2017 Aug;131(4):304-11. doi: 10.1037/bne0000201.
The bed nucleus of the stria terminalis (BNST) is a region of the extended amygdala that is implicated in addiction, anxiety, and stress related behaviors. This region has been identified in mediating the aversive state of naloxone-precipitated morphine withdrawal (MWD) and cannabinoid Type I (CB1) receptors have been found to modulate neurotransmission within this region. Previous findings suggest that the CB1 antagonist/inverse agonist, AM251, administered systemically or by infusion into the central nucleus of the amygdala (CeA) prevented the aversive affective properties of MWD as measured by conditioned place aversion learning. As well, when administered systemically or by infusion into the basolateral nucleus of the amygdala (BLA) or the interoceptive insular cortex, the monoaclyglycerol lipase (MAGL) inhibitor, MJN110 (which elevates 2-arachidonlyglycerol), also prevented a naloxone-precipitated MWD induced place aversion. Given the connectivity of these regions and the BNST, the present study sought to determine whether cannabinoid modulation of the BNST would also prevent the affective properties of naloxone precipitated MWD-induced place aversion learning. Prior to conditioning trials, rats received intra-BNST infusions of AM251, in Experiment 1, or MJN110 in Experiment 2. AM251, but not MJN110, prevented the establishment of the MWD-induced place aversion. The current findings emphasize an important role for the BNST in opioid withdrawal and suggest that the ameliorative effects of systemically administered CB1 antagonists are mediated, in part, by their actions within this region. (PsycINFO Database Record
终纹床核（BNST）是扩展杏仁核的一个区域，与成瘾、焦虑及应激相关行为有关。该区域已被确定在介导纳洛酮诱发的吗啡戒断（MWD）的厌恶状态中起作用，并且发现大麻素I型（CB1）受体可调节该区域内的神经传递。先前的研究结果表明，全身给药或注入杏仁核中央核（CeA）的CB1拮抗剂/反向激动剂AM251，可通过条件性位置厌恶学习测量，预防MWD的厌恶情感特性。同样，当全身给药或注入杏仁核基底外侧核（BLA）或内感受性岛叶皮质时，单酰甘油脂肪酶（MAGL）抑制剂MJN110（可提高2-花生四烯酸甘油酯水平）也可预防纳洛酮诱发的MWD诱导的位置厌恶。鉴于这些区域与BNST的连接性，本研究旨在确定对BNST的大麻素调节是否也能预防纳洛酮诱发的MWD诱导的位置厌恶的情感特性。在条件试验前，实验1中的大鼠接受BNST内注射AM251，实验2中的大鼠接受BNST内注射MJN110。AM251可预防MWD诱导的位置厌恶的形成，但MJN110不能。当前的研究结果强调了BNST在阿片类药物戒断中的重要作用，并表明全身给药的CB1拮抗剂的改善作用部分是由其在该区域的作用介导的。（PsycINFO数据库记录）
