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Blockade of delta-opioid receptors prevents morphine-induced place preference in mice
T Suzuki1, M Yoshiike, H Mizoguchi
1Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Abstract:
Effects of highly selective delta-opioid receptor antagonists on the morphine-induced place preference in ddY and mu 1-opioid receptor deficient CXBK mice were investigated. Pretreatment with naltrindole (NTI: a non-selective delta-opioid receptor antagonist), 7-benzylidenenaltrexone (BNTX: a selective delta 1-opioid receptor antagonist) or naltriben (NTB: a selective delta 2-opioid receptor antagonist) abolished the morphine-induced place preference in ddY mice in a dose-dependent manner. These findings suggest that the morphine-induced place preference may be mediated by both delta 1- and delta 2-opioid receptors. On the other hand, in mu 1-opioid receptor deficient CXBK mice, pretreatment with these selective delta-opioid receptor antagonists did not affect the morphine-induced place preference, although pretreatment with beta-funaltrexamine (beta-FNA: a selective mu-opioid receptor antagonist) significantly inhibited the morphine-induced place preference. [D-Pen2,D-Pen5]enkephalin (DPDPE: a delta 1-opioid receptor agonist) and [D-Ala2,Glu4]deltorphin (deltorphin II: a delta 2-opioid receptor agonist) induced a significant place preference in ddY mice, but not in CXBK mice. These results suggest that delta 1- and delta 2-opioid receptors in the nucleus accumbens that are related to the DPDPE- and deltorphin II-induced place preference may be dysfunctional and/or poor in CXBK mice. These findings also indicate that delta 1- and delta 2-opioid receptors may be involved in the modulation of the reinforcing effect of morphine.
Insights
Morphine
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Opioid receptors, including delta and mu subtypes, play crucial roles in mediating the effects of analgesics and addictive substances.
- Understanding the specific roles of delta-opioid receptor subtypes (delta 1 and delta 2) in morphine's rewarding effects is essential for developing targeted therapies.
Purpose of the Study:
- To investigate the involvement of delta-opioid receptor subtypes in morphine-induced place preference.
- To determine if delta-opioid receptors modulate the reinforcing effects of morphine.
Main Methods:
- Utilized selective delta-opioid receptor antagonists (naltrindole, 7-benzylidenenaltrexone, naltriben) and a mu-1 opioid receptor antagonist (beta-funaltrexamine) in a place preference conditioning paradigm.
- Administered delta-opioid receptor agonists ([D-Pen2,D-Pen5]enkephalin and deltorphin II) to assess their effects in different mouse models.
- Employed ddY mice and mu 1-opioid receptor deficient CXBK mice to differentiate receptor-specific actions.
Main Results:
- Selective delta-opioid receptor antagonists abolished morphine-induced place preference in ddY mice, indicating mediation by both delta 1 and delta 2 receptors.
- In mu 1-opioid receptor deficient CXBK mice, delta-opioid receptor antagonists did not affect morphine preference, but a mu-1 antagonist did, suggesting mu-1 receptor involvement.
- Delta-opioid receptor agonists induced place preference in ddY mice but not in CXBK mice, suggesting potential dysfunction of these receptors in the latter.
- These findings highlight the differential roles of delta and mu opioid receptors in mediating morphine's rewarding effects.
Conclusions:
- Morphine-induced place preference is mediated by both delta 1- and delta 2-opioid receptors.
- Delta-opioid receptors may modulate the reinforcing effects of morphine, with potential dysfunction in mu 1-opioid receptor deficient mice.
- These findings contribute to understanding the complex neurobiological mechanisms underlying opioid reward and addiction.