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Updated: Jul 2, 2026

Operant Sensation Seeking in the Mouse
Published on: November 10, 2010
Genetic correlates of morphine withdrawal in 14 inbred mouse strains
Pamela Metten1, John C Crabbe, John K Belknap
1Portland Alcohol Research Center, Department of Veterans Affairs, Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA. mettenp@ohsu.edu
Abstract:
Male mice from 14 standard inbred strains were exposed to morphine in a sustained released preparation injected subcutaneously. Five hours later withdrawal was precipitated by intraperitoneal injection of naloxone. Mice were tested from 0 to 15 min after naloxone for withdrawal jumping behavior, and then from minute 15-16 for other signs, including boli count, presence of soft stool, lacrimation, "wet dog" shakes, and air chewing. They were also assessed for change in body temperature 17 min after naloxone. Strains differed markedly in the severity of withdrawal for jumping, change in body temperature, and number of fecal boli. Strains also differed in percentage of animals displaying soft stool and air chewing behavior. The other two signs were seen at too low frequency for analysis. Correlations of strain mean withdrawal severity with other responses to morphine and other abused drugs showed that high morphine withdrawal jumping and low change in body temperature were both genetically related to high morphine consumption, but not generally to other measures of morphine withdrawal or morphine sensitivity.
Insights
Genetic differences in mouse strains significantly impact morphine withdrawal symptoms, particularly jumping behavior and body temperature changes. These withdrawal responses are linked to morphine consumption, not general sensitivity.
Area of Science:
- Pharmacology
- Genetics
- Neuroscience
Background:
- Opioid withdrawal is a complex phenomenon with significant individual variability.
- Understanding the genetic underpinnings of withdrawal symptoms is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the genetic basis of morphine withdrawal severity across different inbred mouse strains.
- To identify specific withdrawal behaviors and physiological changes that are genetically influenced by morphine exposure.
Main Methods:
- Male mice from 14 inbred strains were administered a sustained-release morphine preparation.
- Morphine withdrawal was precipitated using naloxone, and various behavioral and physiological signs were assessed.
- Data on jumping behavior, body temperature, fecal boli count, soft stool, lacrimation, "wet dog" shakes, and air chewing were collected.
Main Results:
- Significant strain-dependent differences were observed in morphine withdrawal severity, including jumping behavior, body temperature changes, and fecal boli count.
- Soft stool and air chewing also showed strain-specific frequencies.
- High morphine withdrawal jumping and low body temperature change were genetically correlated with high morphine consumption.
Conclusions:
- Genetic factors play a substantial role in modulating the expression of morphine withdrawal symptoms in mice.
- Specific withdrawal phenotypes, such as jumping and body temperature, are linked to genetic predispositions for morphine consumption.
- These findings highlight the importance of genetic background in opioid withdrawal and may inform future research on addiction treatment.
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