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Updated: Sep 20, 2026
Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Distinct changes in the behavioural effects of morphine and naloxone in CCK2 receptor-deficient mice
Kertu Rünkorg1, Alar Veraksits, Kaido Kurrikoff
1Department of Physiology, Biomedicum, University of Tartu, 19 Ravila Street, Tartu 50411, Estonia.
Abstract:
The effects of morphine, mu-opioid receptor agonist, and naloxone, a non-selective opioid receptor antagonist, in the locomotor activity and place conditioning tests were studied in the CCK(2) receptor-deficient male mice. The exposure of mice to the motility boxes for 3 consecutive days induced a significant inhibition of locomotor activity in the wild-type (+/+) mice compared to homozygous (-/-) animals. The administration of naloxone (10 mg/kg i.p.) to animals, adapted to the motility boxes, induced a significant reduction of locomotor activity in the homozygous (-/-), but not in the wild-type (+/+) mice. Treatment of habituated mice with morphine (10 mg/kg i.p.) caused a stronger increase of locomotor activity in the wild-type (+/+) mice compared to the homozygous (-/-) littermates. In the place preference test the pairing of the preferred side with naloxone (1 and 10 mg/kg i.p.) induced a dose-dependent place aversion in the wild-type (+/+) mice. The treatment with naloxone was less effective in the homozygous (-/-) mice, because the high dose of naloxone (10 mg/kg) tended to shift the preference. The pairing of morphine (3 mg/kg i.p.) injections with the non-preferred side induced a significant place preference both in the wild-type (+/+) and homozygous (-/-) mice. The increased density of opioid receptors was established in the striatum of homozygous (-/-) mice, but not in the other forebrain structures. In conclusion, the targeted invalidation of CCK(2) receptors induces a dissociation of behavioural effects of morphine and naloxone. Morphine-induced place preference remained unchanged, whereas hyper-locomotion was less pronounced in the mutant mice compared to the wild-type (+/+) littermates. By contrast, naloxone-induced place aversion was weaker, but naloxone caused a stronger inhibition of locomotor activity in the homozygous (-/-) mice than in the wild-type (+/+) animals. These behavioural alterations can be explained in the light of data that the targeted mutation of CCK(2) receptors induces distinct changes in the properties of opioid receptors in various brain structures.
Insights
Mice lacking CCK(2) receptors showed altered responses to morphine and naloxone. While morphine
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Cholecystokinin (CCK) plays a role in modulating opioid effects.
- CCK(2) receptors are implicated in various physiological processes, including pain and reward pathways.
Purpose of the Study:
- To investigate the behavioral effects of morphine and naloxone in mice lacking CCK(2) receptors.
- To understand the interaction between CCK(2) receptors and the opioid system in regulating locomotor activity and place conditioning.
Main Methods:
- Utilized CCK(2) receptor-deficient mice and wild-type littermates.
- Assessed locomotor activity in motility boxes over three consecutive days.
- Evaluated place conditioning using place preference and aversion tests with morphine and naloxone administration.
Main Results:
- CCK(2) receptor deficiency altered locomotor responses to naloxone, causing inhibition in mutant mice but not wild-types.
- Morphine-induced hyper-locomotion was reduced in CCK(2) receptor-deficient mice.
- Naloxone-induced place aversion was weaker in mutant mice, while morphine-induced place preference remained intact.
- Increased opioid receptor density was observed in the striatum of mutant mice.
Conclusions:
- Targeted invalidation of CCK(2) receptors dissociates the behavioral effects of morphine and naloxone.
- CCK(2) receptor deficiency alters opioid receptor properties in specific brain structures, leading to distinct behavioral outcomes.
- These findings highlight the role of CCK(2) receptors in modulating opioid system function and behavior.
