Difference in the development of tolerance to morphine and D.-ala2 -Methionine-Enkephalin in C57 BL/6J mice

The analgesic effect elicited by intracerebroventricular (icv) administration of either morphine or d-ala2-methionine-enkephalin (d-ala2-met-enk) was studied during the onset and offset of morphine tolerance in DBA/2J (DBA) and C57 BL/6J (C57) strains of mice. DBA mice become tolerant to the analgesic effect of morphine icv injected after receiving 8 subcutaneous (sc) injections (2 injections daily × 4 days) of the ED50 of morphine for analgesia. In c57 mice tolerance to morphine icv-administered is evident after only a single sc injection of morphine ED50. On the contrary the development of cross-tolerance to the analgesic effect of d-ala2-met-enk is similar in both strains of mice. With respect to the offset period, the recovery of the analgesic effect of morphine and d-ala2-met-enk is slower in C57 than in DBA mice; in C57 mice tolerance to both morphine and d-ala2-met-enk is still present 10 days after morphine withdrawal. These results suggest the existence of a strain dependent rate in the onset of tolerance to the analgesic effect of morphine. C57 mice represent an interesting tool to investigate tolerance to opiates and opioid peptides.