Genetic differences in preferences for morphine and codeine in Lewis and Fischer 344 inbred rat strains.

Preferences for morphine and codeine in two inbred strains of rats, Lewis and Fischer 344 (F344), were systematically investigated using the drug-admixed food (DAF) procedure. Rats were allowed access to food only between 10:00 a.m.-4:00 p.m., but allowed free access to water. The rats were allowed to choose either DAF (0.5 mg/g) or normal food on the first day and then were allowed access only to DAF on the second and third days. After this schedule was repeated 10 times, they were again allowed to choose either DAF or normal food for a successive 8 days. In both strains, preferences for morphine and codeine rapidly increased; the preferences in Lewis rats were significantly higher than those in F344 rats during the daily choice trials. In the range of 0.25 to 1 mg/g for the DAF concentration, there was a negative correlation between the preference and concentration in Lewis and F344 rats, except in the codeine group of F344 rats. When a test dose (60 mg/kg and 30 mg/kg, s.c., in Lewis and F344 rats, respectively) of morphine or codeine was given at 30 min before the beginning of the choice trial, Lewis rats, but not F344 rats, showed a significantly lower preference for the respective drug. The above results indicate that genotype is an important determinant of the degree of preferences for morphine and codeine.