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Morphine withdrawal in mice selectively bred for differential sensitivity to ethanol
Pharmacology, Biochemistry, and Behavior
|January 1, 1982
Summary
Mice selectively bred for alcohol sensitivity show similar withdrawal responses to morphine. Less alcohol-sensitive mice exhibit more severe morphine withdrawal symptoms, suggesting shared neurobiological mechanisms.
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Background:
- Mice selectively bred for differing ethanol (alcohol) sensitivity also exhibit varied seizure severity during alcohol withdrawal.
- These genetic lines provide a valuable model for investigating the neurobiological underpinnings of substance withdrawal.
- Previous research established differences in alcohol withdrawal severity between short sleep (SS) and long sleep (LS) mice.
Purpose of the Study:
- To investigate the responsiveness of SS and LS mice to chronic morphine withdrawal.
- To determine if genetic differences in ethanol sensitivity correlate with differences in opioid withdrawal severity.
- To explore potential shared neurobiological pathways involved in withdrawal from different substances of abuse.
Main Methods:
- Establishment of morphine dependence in SS and LS mice using chronic pellet implantation.
- Precipitation of withdrawal symptoms using naloxone challenge at varying doses.
- Quantification of specific withdrawal behaviors, including jumping and wet dog shakes.
Main Results:
- SS mice, less sensitive to ethanol's hypnotic effects, displayed significantly more jumping and wet dog shakes during naloxone-precipitated morphine withdrawal compared to LS mice.
- The severity of jumping behavior was dose-dependent on naloxone administration in both mouse lines.
- The observed differences in morphine withdrawal severity between SS and LS mice parallel their previously documented differences in alcohol withdrawal seizure severity.
Conclusions:
- Genetic factors influencing ethanol withdrawal severity also impact morphine withdrawal responses in mice.
- Differences in extrapyramidal dopaminergic activity may underlie the observed variations in naloxone-precipitated withdrawal between SS and LS mice, although other mechanisms cannot be excluded.
- These findings suggest conserved neurobiological substrates involved in withdrawal from both alcohol and opioids.
