Khajehpour Lotfollah, Rezayof Ameneh, Zarrindast Mohammad-Reza
Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.
Eur J Pharmacol. 2008 Apr 28;584(2-3):343-51. doi: 10.1016/j.ejphar.2008.02.030. Epub 2008 Feb 19.
The present study evaluated the possible role of nicotinic acetylcholine receptors of the dorsal hippocampus on morphine-induced amnesia and morphine state-dependent memory in adult male Wistar rats. The animals were bilaterally implanted with chronic cannulas in the CA1 regions of the dorsal hippocampi, trained in a step-through type passive avoidance task, and tested 24 h after training to measure step-through latency. Results indicate that post-training subcutaneous (s.c.) administration of morphine (2.5-7.5 mg/kg) dose-dependently reduced the step-through latency, showing an amnestic response. Post-training intra-CA1 microinjection of nicotine (0.5-1 microg/rat) decreased significantly the amnesia induced by post-training morphine (7.5 mg/kg). Moreover, co-treatment of mecamylamine (0.5 and 1 microg/rat, intra-CA1) with an ineffective dose of morphine (2.5 mg/kg), immediately after training, caused inhibition of memory retrieval. On the other hand, amnesia produced by post-training morphine (7.5 mg/kg) was reversed by pre-test administration of the opioid that is due to a state-dependent effect. Interestingly, pre-test intra-CA1 microinjection of nicotine (0.25 and 0.5 microg/rat) improved post-training morphine (7.5 mg/kg)-induced retrieval impairment. Moreover, pre-test administration of the same doses of nicotine in combination with a lower dose of morphine (0.5 mg/kg), which had no effects alone, synergistically improved memory performance impaired by post-training morphine. Pre-test injection of mecamylamine (0.5-2 microg/rat) prevented the restoration of memory by pre-test morphine. It is important to note that post-training or pre-test intra-CA1 administration of the same doses of nicotine or mecamylamine, alone did not affect memory retrieval. These results suggest that nicotinic acetylcholine receptors of the hippocampal CA1 regions may play an important role in morphine-induced amnesia and morphine state-dependent memory.
本研究评估了成年雄性Wistar大鼠背侧海马区烟碱型乙酰胆碱受体在吗啡诱导的失忆及吗啡状态依赖性记忆中可能发挥的作用。动物双侧海马背侧CA1区植入慢性套管，在一步通过式被动回避任务中进行训练，并在训练后24小时进行测试以测量通过潜伏期。结果表明，训练后皮下注射吗啡（2.5 - 7.5毫克/千克）剂量依赖性地缩短通过潜伏期，表现出失忆反应。训练后CA1区内微量注射尼古丁（0.5 - 1微克/只大鼠）显著降低了训练后吗啡（7.5毫克/千克）诱导的失忆。此外，训练后立即将美加明（0.5和1微克/只大鼠，CA1区内注射）与无效剂量的吗啡（2.5毫克/千克）共同处理，导致记忆提取受到抑制。另一方面，训练后吗啡（7.5毫克/千克）产生的失忆通过测试前给予阿片类药物得以逆转，这是由于状态依赖性效应。有趣的是，测试前CA1区内微量注射尼古丁（0.25和0.5微克/只大鼠）改善了训练后吗啡（7.5毫克/千克）诱导的提取损伤。此外，测试前给予相同剂量的尼古丁与较低剂量的吗啡（0.5毫克/千克，单独使用无效果）联合使用，协同改善了训练后吗啡损害的记忆表现。测试前注射美加明（0.5 - 2微克/只大鼠）阻止了测试前吗啡对记忆的恢复。需要注意的是，训练后或测试前在CA1区内给予相同剂量的尼古丁或美加明，单独使用时并不影响记忆提取。这些结果表明，海马CA1区的烟碱型乙酰胆碱受体可能在吗啡诱导的失忆及吗啡状态依赖性记忆中发挥重要作用。
