The effects of morphine (M) on the gastrointestinal transit (charcoal meal test) and pain response were compared in 2 rat models that had been rendered tolerant to M. Tolerance was induced via the oral route in one group and subcutaneous administration (systemic route) in the other group. M and its metabolite concentrations were also analyzed in plasma and brain tissue of tolerant animals. Despite a similar degree of tolerance to the analgesic effects of M and dependence development (withdrawal syndrome) in both groups, a significant degree of M-induced gastrointestinal inhibition was seen in the oral group after 5 days of oral M treatment but not after prolonged systemic M administration. The tolerance development to the intestinal inhibitory effect of systemic M was furthermore reflected by an increase in the ED50 value for acute administered M in rats treated with M systemically for 5 days (1.64 and 19.7 mg/kg respectively). Significantly less tolerance development to the inhibitory effect of M on intestinal transit was noted in rats drinking M solution for the same period of time. Tolerance ratio for acute gastrointestinal inhibitory effect of M was 12.01 and 1.49 (systemic vs oral M administration respectively). The plasma concentration of an active M metabolite - morphine-6-glucuronide was significantly higher after prolonged oral morphine treatment - no significant differences between two models of tolerance development were noted in brain tissue for M and its metabolites. The observed differences in the drug metabolic profiles of the 2 groups might explain the long-lasting effects of prolonged oral M administration on the gastrointestinal transit.
|Original language||English (US)|
|Number of pages||10|
|Journal||Research Communications in Substances of Abuse|
|State||Published - 1992|
All Science Journal Classification (ASJC) codes
- Medicine (miscellaneous)