Different effects of systemic vs oral methods of prolonged morphine administration on gastrointestinal mobility and morphine metabolic pattern in rat

FRANÇAIS :
Des rats sont traités à la morphine soit par voie orale (groupe 0), soit par voie sous-cutanée (groupe S) pendant 5 jours. La tolérance vis à vis des effets analgésiques et la dépendance induite sont similaires dans les 2 groupes. Toutefois, l'inhibition du transit intestinal est conservée dans le groupe 0, pas dans le groupe S. On observe également une concentration plasmatique du métabolite; morphine 6-glucuronide, beaucoup plus élevée dans le plasma des rats du groupe 0. Cette différence pourrait expliquer les effets de l'administration de morphine par voie orale.
ENGLISH :
The effects of morphine (M) on the gastrointestinal transit and pain response were compared in 2 rat models. Tolerance was induced via the oral route in one group and subcutaneous administration 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. 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. (Extract of author's abstract)