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Modification of morphine-induced place preference by diabetes
1Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
European Journal of Pharmacology
|January 16, 1998
Summary
Diabetes enhances morphine-induced place preference in mice, primarily mediated by mu2-opioid receptors. This effect may involve increased delta-opioid receptor activity in diabetic conditions.
Area of Science:
- Neuroscience
- Pharmacology
- Endocrinology
Background:
- Diabetes mellitus is a metabolic disorder with complex effects on the central nervous system.
- Opioid receptors play a crucial role in reward pathways and drug-induced behaviors, including place preference.
- Previous research suggests potential interactions between metabolic state and opioid system function.
Purpose of the Study:
- To investigate the influence of diabetes on morphine-induced place preference in a mouse model.
- To elucidate the specific opioid receptor subtypes involved in morphine reward in both diabetic and non-diabetic states.
- To explore the potential mechanisms underlying enhanced opioid reward in diabetes.
Main Methods:
- Utilized a place preference conditioning paradigm in diabetic and non-diabetic mice.
- Administered varying doses of morphine and assessed conditioned place preference.
- Employed selective opioid receptor antagonists (beta-funaltrexamine, naloxonazine, naltriben, 7-benzylidenenaltrexone) and an agonist (TAN-67) to probe receptor involvement.
- Analyzed the effects of these agents on morphine-induced place preference.
Main Results:
- Morphine induced a dose-related place preference in both diabetic and non-diabetic mice.
- Diabetic mice exhibited a significantly greater morphine-induced place preference compared to non-diabetic controls.
- The mu2-opioid receptor was identified as the primary mediator of morphine-induced place preference.
- Enhanced place preference in diabetic mice was associated with potential up-regulation of delta-opioid receptor-mediated functions, as evidenced by TAN-67 effects.
Conclusions:
- The findings support the hypothesis that mu2-opioid receptor activation is central to morphine-induced place preference.
- Diabetes significantly potentiates morphine reward, suggesting altered opioid system sensitivity.
- Up-regulation of delta-opioid receptor pathways may contribute to the heightened response to morphine in diabetic mice.