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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Ghrelin receptor antagonism of morphine-induced conditioned place preference and behavioral and accumbens dopaminergic sensitization in rats
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Ghrelin receptor antagonism of morphine-induced conditioned place preference and behavioral and accumbens dopaminergic sensitization in rats

机译：大鼠吗啡诱导的调节条件偏好和行为和对昔上大鼠的行为和对昔上的多巴胺能致拮抗症

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Abstract An increasing number of studies over the past few years have demonstrated ghrelin's role in alcohol, cocaine and nicotine abuse. However, the role of ghrelin in opioid effects has rarely been examined. Recently we substantiated in rats that ghrelin growth hormone secretagogue receptors (GHS-R1A) appear to be involved in acute opioid–induced changes in the mesolimbic dopaminergic system associated with the reward processing. The aim of the present study was to ascertain whether a ghrelin antagonist (JMV2959) was able to inhibit morphine-induced biased conditioned place preference and challenge-morphine-induced accumbens dopaminergic sensitization and behavioral sensitization in adult male rats. In the place preference model, the rats were conditioned for 8 days with morphine (10?mg/kg s.c.). On the experimental day, JMV2959 (3 and 6?mg/kg i.p.) or saline were administered before testing. We used in?vivo microdialysis to determine changes of dopamine and its metabolites in the nucleus accumbens in rats following challenge-morphine dose (5?mg/kg s.c.) with or without JMV2959 (3 and 6?mg/kg i.p.) pretreatment, administered on the 12th day of spontaneous abstinence from morphine repeated treatment (5 days, 10–40?mg/kg). Induced behavioral changes were simultaneously monitored. Pretreatment with JMV2959 significantly and dose dependently reduced the morphine-induced conditioned place preference and significantly and dose dependently reduced the challenge-morphine-induced dopaminergic sensitization and affected concentration of by-products associated with dopamine metabolism in the nucleus accumbens. JMV2959 pretreatment also significantly reduced challenge-morphine-induced behavioral sensitization. Our present data suggest that GHS-R1A antagonists deserve to be further investigated as a novel treatment strategy for opioid addiction. Highlights ? Ghrelin antagonism reduced morphine-induced rat accumbens dopaminergic sensitization. ? Ghrelin antagonism reduced morphine-induced behavioral sensitization in rats. ? Ghrelin antagonism reduced morphine-induced conditioned place preference in rats.
机译：摘要在过去几年中越来越多的研究已经证明了Ghrelin在酒精，可卡因和尼古丁滥用中的作用。然而，Ghrelin在阿片类药物中的作用很少被检查。最近，我们在大鼠证实，认为Ghrelin生长激素促泌胞受体（GHS-R1a）似乎参与急性阿片类药物诱导与奖励加工相关的培养基多巴胺能系统的变化。本研究的目的是确定Ghrelin拮抗剂（JMV2959）是否能够抑制吗啡诱导的偏置条件偏好和挑战 - 吗啡诱导的成年雄性大鼠的转移性多巴胺能致敏和行为致敏。在偏好模型中，用吗啡（10×mg / kg s.）将大鼠调节8天。在实验日，在测试前施用JMV2959（3和6？Mg / kg I.P.）或盐水。我们使用的是在攻击 - 吗啡剂量（5？mg / kg sc）的大鼠中测定多巴胺和其代谢物中的多巴胺和其代谢物的变化，所述多巴胺在攻击 - 吗啡剂量（5？mg / kg sc），或没有JMV2959（3和6？Mg / kg IP）预处理，施用在与吗啡的自发禁欲的第12天反复治疗（5天，10-40毫克/千克）。同时监测诱导的行为变化。用JMV2959预处理显着且剂量依赖性降低了吗啡诱导的条件偏好，显着依赖性地减少了与细胞核尿嘧啶中的多巴胺代谢相关的挑战 - 吗啡诱导的多巴胺能致敏和受影响的副产物。 JMV2959预处理也显着降低了挑战 - 吗啡诱导的行为敏化。我们现在的数据表明，GHS-R1A拮抗剂应该进一步调查作为阿片类药物成瘾的新型治疗策略。强调 ？ Ghrelin拮抗作用减少了吗啡诱导的大鼠口交多巴胺能致敏。还Ghrelin拮抗剂降低了吗啡诱导的大鼠行为致敏。还Ghrelin拮抗作用降低了吗啡诱导的大鼠条件偏好。

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