A further assessment of a role for Toll-like receptor 4 in the reinforcing and reinstating effects of opioids.
A further assessment of a role for Toll-like receptor 4 in the reinforcing and reinstating effects of opioids.
复制标题
进一步评估 Toll 样受体 4 在阿片类药物增强和恢复作用中的作用。
DOI：
10.1097/fbp.0000000000000474
复制
发表时间：
2020
影响因子：
1.6
通讯作者：
Zanettini,Claudio
中科院分区：
文献类型：
--
作者：
Yue,Kai;Tanda,Gianluigi;Katz,JonathanL;Zanettini,Claudio
The Toll-like receptor 4 (TLR4) antagonists,(+)-naloxone and (+)-naltrexone, have been reported to decrease self-administration of opioids in rats and to reduce other preclinical indicators of abuse potential. However, under the self-administration conditions studied, the effects of TLR4 antagonists were not reinforcer selective, questioning the involvement of those receptors and their mediated inflammatory response specifically in opioid abuse. The objectives of the current study were to further characterize the reinforcer specificity of TLR4 antagonism in opioid self-administration and to explore its effects in a preclinical model of craving/relapse. The TLR4 antagonist (+)-naltrexone decreased responding in rats trained to self-administer the µ-opioid receptor agonist remifentanil, but with a potency that was not significantly different from that observed in another group of subjects in which responding was maintained by food reinforcement. Responding reinstated by heroin injection was decreased by (+)-naltrexone; however, a similar reduction was not reproduced with the administration of another TLR4 antagonist, lipopolysaccharide from Rhodobacter sphaeroides, administered into the NAcc shell. Thus, TLR4 antagonists lacked reinforcer selectivity in reducing opioid self-administration and were not uniformly effective in a model of craving/relapse, suggesting limitations on the development of (+)-naltrexone or TLR4 antagonists as treatments for opioid abuse.
