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Updated: Feb 6, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Over-expression of CCK1 Receptor Reverse Morphine Dependence
Lijing Hao1,2, Di Wen1, Hongyan Gou1,3
11Department of Forensic Medicine, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Medical University, Shijiazhuang, 050017 Hebei Province People's Republic of China.
Abstract:
Studies demonstrated that cholecystokinin (CCK) system involved in morphine dependence and withdrawal. Our previous study showed that endogenous CCK system were up-regulated after chronic morphine exposure. Additionally, CCK1 receptor significantly blocked the inhibitory effect of exogenous CCK-8 on morphine dependence, but CCK2 receptor appears to be necessary for low concentrations of endogenous CCK to potentiate morphine dependence. Therefore, CCK1R and CCK2R function differently in chronic morphine dependence, but the mechanism is still unclear. In this study, HEK-293 cells co-transfected with µ-opioid receptors (HEK293-hMOR) and CCK1R or CCK2R were established. Cells were treated with 10 µM morphine for 6, 12, 16, 24 h and 100 µM naloxone precipitation for 15 min. cAMP overshoot was appeared at 12 h and was increased time dependently after morphine exposure in HEK293-hMOR cells. The cAMP overshoot did not appear in CCK1R-overexpressing HEK293-hMOR cells, while still appeared in CCK2R-overexpressing HEK293-hMOR cells. Over-expression of CCK1R reversed CREB and ERK1/2 activation in HEK293-hMOR cells exposed to morphine. Our study identifies over-expression of CCK1R significantly blocked morphine dependence, which was related with phosphorylation of CREB, and ERK1/2 signaling activation. While over-expression of CCK2R promoted morphine dependence, which was related with phosphorylation of CREB but not ERK1/2 signaling activation.
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