Oxytocin blocks the development of heroin-fentanyl cross-tolerance in mice.
The development of cross-tolerance to an analgesic effect was observed between two mu-receptor agonists, heroin and fentanyl. Repeated treatments with heroin twice a day for 4 days resulted in a decreased nociceptive effect to fentanyl on day 5. The fentanyl dose-response line shifted to the right, and was considered to be a sign of the development of cross-tolerance. Peripheral treatment with oxytocin did not block the development of heroin-fentanyl cross-tolerance. However, intracerebroventricular administration of oxytocin blocked the development of tolerance, causing a leftward shift in the dose-response curve and supporting the assumption that oxytocin blocks the development of heroin-fentanyl cross-tolerance via CNS mechanisms.
Department of Pathophysiology, Albert Szent-Györgyi, Medical University, Szeged, Hungary.
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M
Kriván
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Szabó
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Z
Sarnyai
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GL
Kovács
G
G
Telegdy
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005283:Fentanyl / Q000494:pharmacology*; D003932:Heroin / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010121:Oxytocin / Q000008:administration & dosage / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects
D000701:Analgesics, Opioid; D010121:Oxytocin; D003932:Heroin; D005283:Fentanyl