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Updated: May 8, 2026
Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Effects of cholecystokinin-8 on morphine-induced spatial reference memory impairment in mice
Shengchang Yang1, Di Wen, Mei Dong
1Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Shijiazhuang 050017, PR China.
Abstract:
Acute and chronic exposure to opiate drugs impaired various types of memory processes. To date, there is no preventive treatment for opiate-induced memory impairment and the related mechanism is still unclear. CCK-8 is the most potent endogenous anti-opioid peptide and has been shown to exert memory-enhancing effect, but the effect of CCK-8 on morphine-induced memory impairment has not been reported. By using Morris water maze, we found that escape latency to the hidden platform in navigation test was not influenced, but performance in the probe test was seriously poor in morphine dependency mice. Amnesia induced by chronic morphine treatment was significantly alleviated by pre-treatment with CCK-8 (0.01, 0.1 and 1 μg, i.c.v.), and CCK-8 (0.1 and 1 μg, i.c.v.) treatment alone could improve performance in either navigation or probe test. Furthermore, Golgi-Cox staining analysis revealed that pre-treatment with CCK-8 (1 μg, i.c.v.) reversed spine density decreased in CA1 region of hippocampus in morphine dependency mice, and CCK-8 (1 μg, i.c.v.) alone obviously increased spine density in CA1. Our findings conclude spine density change in CA1 region of hippocampus may be the structural plasticity mechanism which is responsible for enhancing effect of CCK-8 on spatial reference memory. Therefore, CCK-8 could effectively improve memory impairment in morphine dependency mice.
Insights
Cholecystokinin-8 (CCK-8) can alleviate memory impairment caused by morphine dependence. This peptide may enhance spatial memory by increasing hippocampal spine density, offering a potential treatment for opiate-induced memory deficits.
Area of Science:
- Neuroscience
- Pharmacology
- Memory Research
Background:
- Opiate drugs, such as morphine, are known to impair memory processes.
- Current treatments for opiate-induced memory impairment are lacking, and the underlying mechanisms remain unclear.
- Cholecystokinin-8 (CCK-8), an endogenous anti-opioid peptide, has demonstrated memory-enhancing properties.
Purpose of the Study:
- To investigate the effect of CCK-8 on morphine-induced memory impairment.
- To explore the potential mechanism of CCK-8's effect on spatial memory.
Main Methods:
- Morris water maze test to assess spatial learning and memory in morphine-dependent mice.
- Intracerebroventricular (i.c.v.) administration of CCK-8.
- Golgi-Cox staining to analyze hippocampal CA1 spine density.
Main Results:
- Morphine dependency significantly impaired performance in the probe test of the Morris water maze.
- Pre-treatment with CCK-8 (0.01, 0.1, and 1 μg, i.c.v.) significantly alleviated morphine-induced memory amnesia.
- CCK-8 (0.1 and 1 μg, i.c.v.) alone improved performance in navigation and probe tests.
- CCK-8 (1 μg, i.c.v.) reversed the decrease in hippocampal CA1 spine density caused by morphine dependency and increased spine density on its own.
Conclusions:
- CCK-8 effectively improves spatial reference memory in morphine-dependent mice.
- Increased spine density in the hippocampal CA1 region is a potential structural plasticity mechanism underlying CCK-8's memory-enhancing effects.
- CCK-8 presents a promising therapeutic candidate for opiate-induced memory impairment.
