Effect of oxytocin on acute enkephalin tolerance in mice.

Intracerebroventricular (i.c.v.) administration of a test dose of 0.5 microgram D-Met2-Pro5-enkephalinamide (ENK) resulted in analgesia. Acute tolerance developed if a tolerance-inducing high dose of 5 micrograms ENK was administered i.c.v. prior to the test dose. Tolerance appeared as a reduction of the analgesic effect of the test dose. Subcutaneous (s.c.) injection of oxytocin (OXT) inhibited the development of tolerance. It is suggested that OXT is able to modify the development of tolerance to enkephalins, which are ligands of delta-opiate rather than mu-opiate receptors.