Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Neuroscience Research Center, Institute of Neuropharmacology, Department of Physiology and Pharmacology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Clin Exp Pharmacol Physiol. 2019 Aug;46(8):711-722. doi: 10.1111/1440-1681.13090. Epub 2019 May 2.
Minocycline as a member of the tetracycline family is a lipophilic broad-spectrum antibiotic, which can display some non-antibiotic properties such as antioxidant, antiapoptosis, neuroprotection and modulation of pharmacological traits of drugs of abuse (ie, reward, sensitization and/or analgesia). Thus, the aim of the present study was to investigate the effect of intracerebroventricular (ICV) injection of minocycline on morphine-induced memory impairment and motor function in male Wistar rats. The behavioural responses were measured by a passive avoidance test for evaluating memory, and in the open field for studying motor function. Furthermore, the expression of Phospho-cAMP response element-binding protein (P-CREB) and c-Fos were assessed using immunohistochemistry in the dorsal hippocampus and basolateral amygdala (BLA). Our results showed that morphine dose-dependently impairs memory consolidation, but not motor function. Maximum effect was achieved with morphine at dose of 5 mg/kg. Pretreatment with ICV injection of minocycline (50 μg/rat) prevented morphine-induced memory impairment, but there was no effect on motor function. The results of immunohistochemistry analysis demonstrated that morphine decreased expression of P-CREB positive cells compared to saline control group in the BLA, but not in the dorsal hippocampus. On the other hand, pretreatment of animals with ICV injection of minocycline increased the expression of P-CREB in both brain areas. Moreover, there was no significant change in the expression of c-Fos positive cells in above-mentioned regions. In summary, our results indicated that pretreatment with ICV injection of minocycline prevented morphine-induced memory impairment and increased P-CREB expression in the dorsal hippocampus and BLA, which may explain its memory improvement property.
米诺环素是四环素类家族的一员，是一种亲脂性广谱抗生素，它可以表现出一些非抗生素特性，如抗氧化、抗细胞凋亡、神经保护和调节药物滥用的药理特性（即奖励、敏化和/或镇痛）。因此，本研究旨在探讨侧脑室（ICV）注射米诺环素对雄性 Wistar 大鼠吗啡诱导的记忆障碍和运动功能的影响。通过被动回避试验评估记忆，通过旷场试验研究运动功能来测量行为反应。此外，使用免疫组织化学法评估背侧海马和基底外侧杏仁核（BLA）中磷酸化 cAMP 反应元件结合蛋白（P-CREB）和 c-Fos 的表达。我们的结果表明，吗啡剂量依赖性地损害记忆巩固，但不损害运动功能。最大作用是用 5mg/kg 的吗啡实现的。预先 ICV 注射米诺环素（50μg/大鼠）可预防吗啡引起的记忆障碍，但对运动功能没有影响。免疫组织化学分析的结果表明，与生理盐水对照组相比，吗啡降低了 BLA 中 P-CREB 阳性细胞的表达，但对背侧海马没有影响。另一方面，预先用 ICV 注射米诺环素处理动物增加了两个脑区中 P-CREB 的表达。此外，上述区域中 c-Fos 阳性细胞的表达没有显著变化。总之，我们的结果表明，预先 ICV 注射米诺环素可预防吗啡引起的记忆障碍，并增加背侧海马和 BLA 中 P-CREB 的表达，这可能解释了其改善记忆的特性。
