Abstract
The development of cross-tolerance to an analgesic effect has been observed between a μ-receptor agonist, heroin, and a δ-receptor agonist, Met 2-Pro 5-enkephalinamide. Repeated treatments with heroin twice a day for 4 days resulted in a decreased nociceptive effect to enkephalin on day 5. The enkephalin dose-response line was shifted to the right, considered a sign of the development of cross-tolerance. Peripheral treatment with oxytocin blocked the development of heroin-enkephalin cross-tolerance. A similar effect was observed after intracerebroventricular administration oxytocin, supportinng our assumption that oxytocin blocks the development of heroin-enkephalin cross-tolerance via CNS mechanisms.
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