CCK-8 Inhibits Acute Morphine-induced Spatial Reference Memory Impairment in Mice

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Administration of morphine may impair learning and memory processes. Cholecystokinin has been reported to be involved in various types of memory, and our previous study found that Cholecystokinin octapeptide attenuates spatial memory impairment in chronic morphine-treated mice. However, the effect of CCK-8 on acute morphine-induced memory impairment is not clear. In this study, effect of acute CCK-8 and morphine on spatial reference memory was evaluated using Morris water maze in KM mice. Acetylcholine (Ach) content was measured using ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC–MS/MS). Pre-training with morphine (5, 10 mg/kg, i.p.) significantly impaired spatial reference memory acquisition without disturbing the performance in the visible platform task, while pre-test morphine has no effect on memory retrieval. Pre-training (0.01, 0.1 and 1 μg, i.c.v.) or pre-test (0.1 and 1 μg, i.c.v.) of CCK-8 facilitated spatial reference memory acquisition and retrieval, respectively. CCK-8 (0.1 and 1 μg) significantly attenuated memory loss by pre-training morphine. Furthermore, CCK-8 (1 μg, i.c.v) increased acetylcholine contents of hippocampus in saline or morphine-treated mice. Our study identifies CCK-8 reversed spatial reference memory loss induced by acute morphine, and the mnemonic effect could be related to the facilitation of CCK-8 on memory acquisition and retrieval through accelerating acetylcholine release in hippocampus.

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All of the authors contributed to the writing of the manuscript and approved the final version. This study was supported in part by grants from the Natural Science Foundation of China (No. 81172900, 30672355), the Applied Basic Research Key Program of Hebei Province (No. 10966911D) and the Natural Science Foundation of Hebei Province (No. C2007000826).

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Correspondence to Chunling Ma or Bin Cong.

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Shengchang Yang, Ting Feng, Dong Li, Di Wen, Chenteng Yang, Chunling Ma and Bin Cong confirmed that they have no conflicts of interest.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Yang, S., Feng, T., Li, D. et al. CCK-8 Inhibits Acute Morphine-induced Spatial Reference Memory Impairment in Mice. Int J Pept Res Ther 23, 357–369 (2017) doi:10.1007/s10989-016-9568-y

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  • Cholecystokinin octapeptide
  • Morphine
  • Spatial reference memory
  • Morris water maze
  • Acetylcholine