In the present study the effect of ghrelin or ghrelin/nicotine injection into the anterior ventral tegmental area (aVTA) on morphine-induced amnesia in passive avoidance learning have been evaluated. Also, the role of the aVTA nicotinic receptors in possible ghrelin-induced effects has been investigated. All animals were bilaterally implanted with chronic cannulas in the aVTA. A step-through type passive avoidance task was used for measurement of memory. We found that post-training subcutaneous (s.c.) injection of morphine (0.5-7.5 mg/kg) dose-dependently reduced the step-through latency, indicating morphine-induced amnesia. Post-training bilateral infusion of ghrelin (0.3, 1.5 and 3 nmol/μl) in a dose-dependent manner reversed amnesia induced by morphine (7.5 mg/kg, s.c.). Furthermore, reversal effect of ghrelin (3 nmol/μl) was blocked by pre-treatment of intra-aVTA administration of mecamylamine (1-3 μg/rat), a nicotinic acetylcholine receptor antagonist. Intra-aVTA administration of the higher dose of mecamylamine (3 μg/rat) into the aVTA by itself decreased the step-through latency and induced amnesia. In addition, post-training intra-aVTA administration of nicotine (0.25, 0.5, 1 μg/rat) which alone cannot affect memory consolidation, decreased significantly the amnesia induced by morphine (7.5 mg/kg, s.c.). Co-treatment of an ineffective dose of ghrelin (0.3 nmol/μl) with an ineffective dose of nicotine (0.25 μg/rat) significantly increased step-through latency of morphine (7.5 mg/kg, s.c.) treated animals, indicating the synergistic effect of the drugs. Taken together, our results suggest that intra-aVTA administration of ghrelin reversed morphine-induced amnesia and that ghrelin interacts synergistically with nicotine to mitigate morphine-induced amnesia.

中文翻译：

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前腹侧被盖区尼古丁-生长素释放肽联合注射对吗啡所致健忘症的协同改善作用

在本研究中，评估了在前腹侧被盖区 (aVTA) 注射生长素释放肽或生长素释放肽/尼古丁对被动回避学习中吗啡诱发的健忘症的影响。此外，已经研究了 aVTA 烟碱受体在可能的生长素释放肽诱导作用中的作用。所有动物在 aVTA 中双侧植入慢性插管。步进式被动回避任务用于测量记忆。我们发现训练后皮下 (sc) 注射吗啡 (0.5-7.5 mg/kg) 剂量依赖性地降低了潜伏期，表明吗啡引起的健忘症。训练后双侧输注生长素释放肽（0.3、1.5 和 3 nmol/μl）以剂量依赖性方式逆转吗啡（7.5 mg/kg，sc）诱发的健忘症。此外，ghrelin (3 nmol/μl) 的逆转作用被 aVTA 内施用美加明（1-3 μg/大鼠）（一种烟碱型乙酰胆碱受体拮抗剂）的预处理所阻断。aVTA 内将较高剂量的美加明 (3 μg/大鼠) 单独给药到 aVTA 中可降低步进潜伏期并诱发健忘症。此外，单独使用不能影响记忆巩固的尼古丁（0.25、0.5、1 μg/大鼠）的训练后 aVTA 给药显着降低了吗啡（7.5 mg/kg，sc）诱发的健忘症。无效剂量的生长素释放肽 (0.3 nmol/μl) 与无效剂量的尼古丁 (0.25 μg/大鼠) 的共同治疗显着增加了吗啡 (7.5 mg/kg, sc) 治疗动物的潜伏期，表明协同作用的药物。综合起来，