Abstract：
Previous studies from our laboratory have shown sex differences in the behavioral, molecular, and neurochemical manifestations of morphine withdrawal and they were related to an increased sensitivity to morphine effects in males. In addition, we observed an interaction between the GABAergic and opioid systems that could also be sex-dependent. Baclofen, a GABAB receptor agonist, prevented the somatic expression and the molecular and neurochemical changes induced by morphine withdrawal syndrome in mice. On the contrary, little is known about baclofen effects in the rewarding properties of morphine in male and female mice. The present study aimed to explore the effect of baclofen (1, 2 and 3 mg/kg, i.p.) pretreatment in the rewarding effects induced by morphine (7 mg/kg, s.c.) and its effect on c-Fos and brain-derived neurotrophic factor (BDNF) expression induced by the rewarding properties of morphine in prepubertal male and female mice. Baclofen (2 mg/kg) pretreatment prevented the rewarding effects of morphine only in male mice, while baclofen (3 mg/kg) reduced these effects in both sexes. Moreover, the rewarding effects of morphine were associated with a decrease of BDNF and c-Fos expression cingulate cortex, nucleus accumbens shell, cornu ammonis 1 (CA1), and cornu ammonis 3 (CA3) areas of the hippocampus only in male mice. In addition, baclofen pretreatment prevented these changes in BDNF, but not in c-Fos expression. In conclusion, our results show that GABAB receptors have a regulatory role in the rewarding effects of morphine that could be of interest for a potential future therapeutic application in opioid use disorders.
摘要：
我们实验室的先前研究表明行为上的性别差异，分子，和吗啡戒断的神经化学表现，它们与男性对吗啡作用的敏感性增加有关。此外,我们观察到GABA能和阿片样物质系统之间的相互作用也可能是性别依赖性的.巴氯芬,一种GABAB受体激动剂，预防了吗啡戒断综合征小鼠的体细胞表达以及分子和神经化学变化。相反,关于巴氯芬在雄性和雌性小鼠吗啡的奖励特性中的作用知之甚少。本研究旨在探讨巴氯芬(1、2和3mg/kg，i.p.）预处理在吗啡（7mg/kg，s.c.）及其对吗啡在青春期前雄性和雌性小鼠中的奖励特性诱导的c-Fos和脑源性神经营养因子（BDNF）表达的影响。巴氯芬（2mg/kg）预处理仅在雄性小鼠中阻止了吗啡的奖励作用，而巴氯芬（3mg/kg）降低了两性的这些作用。此外，吗啡的奖励作用与BDNF和c-Fos表达减少有关扣带皮质，伏隔核壳，玉米氨1(CA1)，仅在雄性小鼠中海马的玉米氨3（CA3）区域。此外,巴氯芬预处理阻止了BDNF的这些变化，但不是在c-Fos表达式中。总之,我们的研究结果表明,GABAB受体在吗啡的奖励效应中具有调节作用,这对于阿片类药物使用障碍的潜在未来治疗应用可能具有重要意义.
