Development of tolerance to the effect of dermorphin on gastric emptying in the rat.

The development of tolerance to the effect of dermorphin on gastric emptying (G.E.) induced by repeated subcutaneous (s.c.), intracerebroventricular (i.c.v.) injections or by i.c.v. infusion of this peptide, was studied in rats. Dermorphin produced a delay in G.E. when it was injected i.c.v. or s.c., but when for 5 days rats were injected twice daily with the same dose of peptide, the acute i.c.v. injection of dermorphin no longer produced a significant delay in G.E. demonstrating an establishment of tolerance to this effect. However, 10 days were necessary to establish tolerance to s.c. injection of the peptide. When dermorphin was i.c.v. infused by a minipump, tolerance to delay of G.E. was inversely proportional to infusion time and it took 2 days to establish tolerance to this peripheral effect. These data suggest the possibility that different development mechanisms: of dermorphin-induced tolerance seem to exists for gastrointestinal responses as compared to other effects of dermorphin, analgesia and catalepsy.