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Development of physical dependence on morphine not accompanied with tolerance formation
1Department of Pharmacology, Faculty of Pharmaceutical Sciences, Nagasaki University, Japan.
Journal of Pharmacobio-Dynamics
|August 1, 1992
Summary
Adrenergic blockers like phentolamine and propranolol suppressed morphine tolerance in mice but did not prevent physical dependence. This suggests morphine
Area of Science:
- Pharmacology
- Neuroscience
- Drug Tolerance
Background:
- Repeated morphine administration can lead to tolerance and physical dependence.
- The precise mechanisms underlying these effects are not fully understood.
- Adrenergic pathways are implicated in opioid effects.
Purpose of the Study:
- To investigate the role of adrenergic blockers in modulating morphine tolerance and physical dependence.
- To determine if tolerance and dependence are dissociable phenomena.
Main Methods:
- Mice received daily subcutaneous injections of morphine (10 mg/kg).
- Adrenergic blockers (phentolamine or propranolol, 10 mg/kg i.p.) were co-administered.
- Development of tolerance was assessed, and physical dependence was evaluated via naloxone-precipitated abstinence signs.
Main Results:
- Combined administration of phentolamine or propranolol with morphine significantly suppressed the development of morphine tolerance.
- The same treatment regimen failed to prevent the emergence of physical dependence, as indicated by naloxone-induced withdrawal symptoms.
- These findings demonstrate a dissociation between morphine tolerance and physical dependence.
Conclusions:
- Adrenergic receptor blockade can inhibit the development of morphine tolerance.
- Morphine tolerance and physical dependence are distinct processes.
- Targeting adrenergic pathways may offer strategies for managing opioid tolerance.