A comparison of morphine-induced locomotor activity and mesolimbic dopamine release in C57BL6, 129Sv and DBA2 mice

Inbred mouse strains show marked variations in morphine-induced locomotion and reward behaviors. As increases in mesolimbic dopamine release and locom otion have been implicated as being critical aspects of drug-seeking and re ward-related behaviors, the present study sought to determine the relations hip between morphine-induced changes in locomotion and mesolimbic dopamine release. Freely moving microdialysis of the ventral striatum was performed in mouse strains chosen on the basis of their documented differences in loc omotor and reward response to morphine (C57BL6 and DBA2) and use in the pro duction of genetically modified mice (129Sv). Both C57BL6 and 129Sv mice sh owed significant increases in locomotion and ventral striatal extracellular dopamine levels following subcutaneous morphine administration (3 mg/kg), with the former strain showing the largest increase in both parameters. Ven tral striatal extracellular DA levels increased in DBA2 mice to a similar e xtent as 129Sv mice following morphine administration, despite this strain showing no locomotor response. Intrastrain analysis found no correlation be tween morphine-induced locomotion and mesolimbic dopamine release in any of the strains studied. Thus, no universal relationship between morphine-indu ced mesolimbic dopamine release and locomotion exists between, and particul arly within, inbred mouse strains. Furthermore, morphine-induced increases in mesolimbic activity correlate negatively with the rewarding potential of morphine described in previously reported conditioned place preference stu dies.