OXYTOCIN BLOCKS THE DEVELOPMENT OF HEROIN FENTANYL CROSS-TOLERANCE INMICE

The development of cross-tolerance to an analgesic effect was observed between two mu-receptor agonists, heroin and fentanyl. Repeated treat ments with heroin twice a day for 4 days resulted in a decreased nocic eptive effect to fentanyl on day 5. The fentanyl dose-response line sh ifted 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, intracere broventricular administration of oxytocin blocked the development of t olerance, causing a leftward shift in the dose-response curve and supp orting the assumption that oxytocin blocks the development of heroin-f entanyl cross-tolerance via CNS mechanisms.