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Endogenous oxytocin inhibits morphine tolerance through limbic forebrain oxytocin receptors
1Institute of Pathophysiology, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Abstract:
It has previously been shown that endogenous oxytocin (OXT) inhibits the development of acute morphine tolerance. The role of OXT receptors in the central nervous system (CNS) was therefore studied by using a specific OXT receptor antagonist, N-acetyl-(2-O-methyltyrosin)-OXT (ACME-OXT). ACME-OXT (1 pg) was injected into the posterior olfactory nucleus, central amygdaloid nucleus, ventral hippocampus, caudate nucleus or lateral cerebral ventricle. The antagonist facilitated the development of tolerance to morphine when injected into the posterior olfactory nucleus, central amygdaloid nucleus or ventral hippocampal areas, which are known to contain OXT binding sites. When administered into the caudate nucleus (with no OXT binding sites) or the lateral cerebral ventricle, it had no effect on morphine tolerance. Our results suggest that the limbic forebrain OXT receptors play an important inhibitory role in adaptive responses to morphine.
Insights
Endogenous oxytocin (OXT) inhibits morphine tolerance. Blocking OXT receptors in specific brain areas, like the limbic forebrain, facilitated morphine tolerance, suggesting OXT
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Endogenous oxytocin (OXT) is known to inhibit acute morphine tolerance.
- The specific role of OXT receptors within the central nervous system (CNS) in this process requires further elucidation.
Purpose of the Study:
- To investigate the function of oxytocin (OXT) receptors in the central nervous system (CNS) regarding morphine tolerance.
- To determine the impact of blocking OXT receptors in distinct brain regions on the development of morphine tolerance.
Main Methods:
- Utilized N-acetyl-(2-O-methyltyrosin)-OXT (ACME-OXT), a selective OXT receptor antagonist.
- Administered ACME-OXT (1 pg) via microinjection into specific CNS sites: posterior olfactory nucleus, central amygdaloid nucleus, ventral hippocampus, caudate nucleus, and lateral cerebral ventricle.
Main Results:
- ACME-OXT administration facilitated morphine tolerance when injected into the posterior olfactory nucleus, central amygdaloid nucleus, and ventral hippocampus.
- These brain regions are known to possess OXT binding sites.
- No effect on morphine tolerance was observed when ACME-OXT was injected into the caudate nucleus (lacking OXT binding sites) or the lateral cerebral ventricle.
Conclusions:
- OXT receptors located in the limbic forebrain play a significant inhibitory role in the adaptive responses to morphine.
- Targeting limbic forebrain OXT receptors may offer a strategy to modulate morphine tolerance.