Two inbred rat strains, the Lewis and Fischer 344, differ in certain of their behavioral responses to remains unclear. However, biochemical differences within the mesolimbic dopamine (DA) system of these strains have been reported. In the present study, the effects of acute morphine challenges on DA overflow in the NA were studied using in vivo microdialysis in the freely moving rat. Locomotor activity was studied in separate groups of rats. We found that basal DA release was slightly, but significantly, higher in Fischer rats, compared to Lewis rats. Neither saline nor the 1.0 mg/kg dose of morphine modified DA release in the NA. At 5.0 mg/kg, however, a significant increase in DA overflow was measured. DA release was markedly higher in Fischer rats at the 10 to 40 min interval with a peak increase of 553% at 30 min. In contrast, the peak increase in Lewis rats (336%) occurred at the 20 min time point. There was no significant difference between strains in locomotor activity during the habituation test. However, the time course of morphine's effects differed between the two strains. At present, it is not clear if pharmacokinetic or pharmacodynamic alterations explain these differences.
