Effects of chronically elevated intake of different concentrations of saccharin on morphine tolerance in genetically selected rats.

Sixty-four LC2-Hi and LC2-Lo female rats were chronically supplied with either water or a solution of 1, 3 or 30 mM of sodium-saccharin. Pain sensitivity, as well as its reduction by a 2.5 mg/kg morphine injection, were measured in a hot-plate test. High saccharin consuming LC2-Hi rats did not exhibit significant morphine-induced analgesia (MIA) compared to baseline, after 38 days of drinking of saccharin, irrespective of concentration. MIA of those rats were maintained on water was significant. In contrast, the low consuming LC2-Lo animals maintained either on water or on 1 and 30 mM saccharin showed significant MIA compared to baseline, following the same exposure period. The findings demonstrate that chronically elevated saccharin intake, activates an endogenous opiate system leading ultimately to cross-tolerance to the analgetic effects of morphine.