Repeated morphine treatment alters cannabinoid modulation of GABAergic synaptic transmission within the rat periaqueductal grey.
Repeated morphine treatment alters cannabinoid modulation of GABAergic synaptic transmission within the rat periaqueductal grey.
复制标题
重复吗啡治疗改变了大麻素对大鼠导水管周围灰质内 GABA 能突触传递的调节。
DOI：
10.1111/bph.12809
复制
发表时间：
2015
影响因子：
7.3
通讯作者：
Vaughan,CW
中科院分区：
文献类型：
--
作者：
Wilson-Poe,AR;Lau,BK;Vaughan,CW
背景和目的大麻素和阿片类药物通过调节中脑导水管周围灰质（PAG）下行镇痛通路中的GABA能突触传递产生抗伤害感受作用。虽然慢性阿片类药物治疗产生阿片类药物耐受性，但最近已显示其可增强PAG内大麻素诱导的抗伤害感受。本研究探讨了重复阿片类药物治疗对阿片类和大麻素突触前调制的GABA能突触传递在PAG中的作用。实验方法从未经治疗的大鼠和反复接受吗啡或盐水预处理的大鼠制备中脑PAG切片。在未处理动物的脑片中，大麻素受体激动剂WIN 55212和μ受体激动剂DAMGO抑制PAG神经元中电诱发GABA A受体介导的抑制性突触后电流（IPSC）IPSC，IC 50分别为30和100 nM。WIN 55212（30 nM）和DAMGO（100 nM）对诱发IPSC的抑制作用在吗啡和盐水处理动物的PAG神经元中相似。大麻素CB 1受体拮抗剂AM 251增加了重复吗啡治疗动物PAG神经元中自发性微型IPSC的频率，但没有盐水治疗动物。DAMGO抑制诱发的IPSCs的增强中存在的AM 251在吗啡-，但不是salin-treated animals.Conclusions和ImplicationsThese结果表明，GABA能突触传递的激动剂诱导的抑制的效率增强吗啡治疗，虽然这是抑制内源性大麻素介导的紧张性抑制。因此，突触传递的内源性大麻素调制可以提供一种替代的镇痛方法在吗啡耐受状态。链接ArticlesThis article is part of a themed section on Opioids：New Pathways to Functional Selectivity.要查看本节中的其他文章，请访问http://dx.doi.org/10.1111/bph.2015.172.issue-2
Background and PurposeCannabinoids and opioids produce antinociception by modulating GABAergic synaptic transmission in a descending analgesic pathway from the midbrain periaqueductal grey (PAG). While chronic opioid treatment produces opioid tolerance, it has recently been shown to enhance cannabinoid‐induced antinociception within the PAG. This study examined the effect of repeated opioid treatment on opioid and cannabinoid presynaptic modulation of GABAergic synaptic transmission in PAG.Experimental ApproachMidbrain PAG slices were prepared from untreated rats, and rats that had undergone repeated morphine or saline pretreatment. Whole‐cell voltage‐clamp recordings were made from neurons within the ventrolateral PAG.Key ResultsIn slices from untreated animals, the cannabinoid receptor agonist WIN55212 and the μ receptor agonist DAMGO inhibited electrically evoked GABAAreceptor‐mediated inhibitory postsynaptic currents (IPSCs) IPSCs in PAG neurons, with IC50s of 30 and 100 nM respectively. The inhibition of evoked IPSCs produced by WIN55212 (30 nM) and DAMGO (100 nM) was similar in PAG neurons from morphine‐ and saline‐treated animals. The cannabinoid CB1receptor antagonist AM251 increased the frequency of spontaneous miniature IPSCs in PAG neurons from repeated morphine‐, but not saline‐treated animals. DAMGO inhibition of evoked IPSCs was enhanced in the presence of AM251 in morphine‐, but not saline‐treated animals.Conclusions and ImplicationsThese results indicate that the efficiency of agonist‐induced inhibition of GABAergic synaptic transmission is enhanced by morphine treatment, although this is dampened by endocannabinoid‐mediated tonic inhibition. Thus, endocannabinoid modulation of synaptic transmission could provide an alternative analgesic approach in a morphine‐tolerant state.Linked ArticlesThis article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2