吗啡对小鼠记忆巩固的影响涉及D1和D2多巴胺受体

Claudio Castellano , Vincenzo Cestari , Simona Cabib , Stefano Puglisi-Allegra
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引用次数: 51

摘要

训练后给药吗啡(0.25、0.5或1 mg/kg)剂量依赖性地损害小鼠抑制性回避反应的保留。该药对记忆保留性能的影响似乎是由于对记忆巩固的影响。事实上,在训练后短时间内(而不是长时间)给药时,也就是说,当记忆痕迹容易受到调节时,就可以观察到这些变化。此外,这些影响不能归因于药物对保持性能的厌恶或奖励或非特异性作用,因为在训练期间未接受足震的小鼠在保持测试中的潜伏期不受训练后药物管理的影响。用选择性D1或D2多巴胺受体拮抗剂SCH 23390和(-)-舒必利进行预处理,其本身无效剂量(分别为0.025和6 mg/kg)可增强吗啡的作用,而选择性D1或D2受体激动剂SKF 38393和LY 171555,其本身无效剂量(分别为5和0.25 mg/kg)可拮抗阿片类药物对记忆巩固的作用。D1和D2受体活性化合物对记忆巩固的影响没有明显差异,这表明D1和D2受体类型与吗啡对记忆巩固的影响相似,与先前报道的结果一致。这些结果讨论了内源性阿片类药物和大脑中涉及记忆过程的DA系统可能的反比关系。
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The effects of morphine on memory consolidation in mice involve both D1 and D2 dopamine receptors

Post-training administration of morphine (0.25, 0.5, or 1 mg/kg) dose-dependently impairs retention of an inhibitory avoidance response in mice. The effects on retention performance induced by the drug appear to be due to an effect on memory consolidation. In fact, they were observed when drugs were given at short, but not long, periods of time after training, i.e., when the memory trace was susceptible to modulation. Moreover, these effects are not to be ascribed to an aversive or a rewarding or nonspecific action of the drugs on retention performance, because the latencies during the retention test of those mice that had not received a footshock during the training were not affected by post-training drug administration. Pretreatment with either selective D1 or D2 dopamine (DA) receptor antagonists SCH 23390 and (-)-sulpiride administered at per se noneffective doses (0.025 and 6 mg/kg, respectively) potentiated the effects of morphine, while either selective D1 or D2 receptor agonists SKF 38393 and LY 171555 at per se noneffective doses (5 and 0.25 mg/kg, respectively) antagonized the effects of the opiate on memory consolidation. No significant differences were evident between the effects of D1 and D2 receptor active compounds, thus suggesting that D1 and D2 receptor types are similarly involved in the effects of morphine on memory consolidation, in agreement with previously reported results. These results are discussed in terms of a possible inverse relationship of endogenous opioid and DA systems in the brain that are involved in memory processes.

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