Related Experiment Video
Updated: Aug 30, 2026
Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
[Development and characteristics of reverse tolerance to repeatedly administered morphine in mice manifested by
Abstract:
Characteristics of changes in ambulatory activity after repeated administration of morphine, 5, 10 or 20 mg/kg s.c., were investigated in male mice of dd strain. The drug was administered 10 times at intervals of 1, 3-4 or 7 days, and the ambulatory activity of each mouse was measured by a tilting-type round activity cage with a 25 cm diameter for 180 min after each administration. Morphine, 5-20 mg/kg induced a dose-dependent increase in the ambulatory activity, and this effect attained to a peak at 60-90 min and persisted for 120-180 min after the administration. An augmentation of sensitivity (a reverse tolerance) to the ambulation-increasing effect of morphine was induced by the repeated administration of 10 and 20 mg/kg morphine, regardless of the intervals. The reverse tolerance achieved the maximum on the 5-6th administration day, and almost the same level of sensitivity was maintained until the 10th administration day. There was no significant difference in the activity counts at the peak time among the groups of mice varying the administration intervals. However, the persistence of increased ambulatory activity tended to be longer in the group of mice given morphine at intervals of 7 days than in the group given it at intervals of 1 day. The reverse tolerance, once produced, attenuated 2 months after the cessation of the repeated administration. However, the ambulatory activity counts did not return to those on the 1st administration day.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Repeated morphine administration in mice increased ambulatory activity, leading to reverse tolerance. This heightened sensitivity persisted even after a two-month cessation, indicating long-term changes in motor activity response.
Area of Science:
- Neuropharmacology
- Behavioral Neuroscience
Context:
- Investigating the effects of repeated morphine administration on motor activity in male dd strain mice.
- Assessing dose-dependent and time-dependent changes in ambulatory behavior following chronic morphine exposure.
Purpose:
- To characterize the alterations in ambulatory activity after repeated morphine administration at varying doses and intervals.
- To determine the development and persistence of tolerance or reverse tolerance to morphine's effects on locomotion.
Summary:
- Morphine (5-20 mg/kg) dose-dependently increased ambulatory activity in mice, peaking at 60-90 minutes.
- Repeated administration of 10 and 20 mg/kg morphine induced reverse tolerance, enhancing sensitivity to its locomotor effects.
- Reverse tolerance peaked by the 5-6th administration and persisted, with longer administration intervals potentially increasing the duration of increased activity.
Impact:
- Reveals the development of reverse tolerance to morphine's locomotor-stimulating effects with repeated exposure.
- Suggests that administration intervals influence the persistence of morphine-induced hyperlocomotion.
- Demonstrates lasting changes in ambulatory activity response to morphine, even after cessation of drug administration.
