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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.
Overexpressing cholecystokinin-1 receptors (CCK1R) blocked morphine dependence by inhibiting CREB and ERK1/2 activation. Conversely, CCK2R overexpression promoted dependence via CREB activation, highlighting distinct roles in opioid addiction mechanisms.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- The cholecystokinin (CCK) system plays a role in morphine dependence and withdrawal.
- Endogenous CCK system is upregulated following chronic morphine exposure.
- CCK1 and CCK2 receptors have distinct, yet unclear, roles in morphine dependence.
Purpose of the Study:
- To investigate the differential mechanisms of CCK1 and CCK2 receptors in morphine dependence.
- To elucidate the signaling pathways involved in CCK receptor modulation of opioid dependence.
Main Methods:
- Established HEK-293 cells co-transfected with human µ-opioid receptors (HEK293-hMOR) and either CCK1R or CCK2R.
- Cells were treated with morphine and naloxone.
- Measured cAMP levels, CREB, and ERK1/2 phosphorylation.
Main Results:
- Morphine-induced cAMP overshoot in HEK293-hMOR cells was abolished by CCK1R overexpression but persisted with CCK2R overexpression.
- CCK1R overexpression reversed morphine-induced CREB and ERK1/2 activation.
- CCK2R overexpression promoted morphine dependence, linked to CREB phosphorylation but not ERK1/2.
Conclusions:
- CCK1R overexpression significantly blocks morphine dependence, associated with the inhibition of CREB and ERK1/2 signaling.
- CCK2R overexpression promotes morphine dependence, linked to CREB phosphorylation, suggesting distinct roles in opioid addiction.
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