Lithium and bupropion antagonise the phasic changes in locomotor activity caused by dopamine infused into the rat nucleus accumbens

Dopamine infused persistently (25 g/24 h for 13 days) into the nucleus accumbens of rat brain caused phasic increases in spontaneous locomotor activity during the period of infusion. This phasic responding was prevented by lithium administered throughout the infusion period in divided doses (3×daily administrations of 2.5 mg/kg IP) or as a continuous IP infusion (7.5 mg/kg/24 h), and by bupropion treatment (5–20 mg/kg 3 × daily). In contrast, imipramine, amitriptyline and nomifensine failed to prevent the phasic locomotor response to dopamine at doses which did not by themselves cause marked motor changes. Locomotor activity was measured using individual photocell cages, and rats preselected to (–)NPA were those initially showing a modest locomotor activity. Fourteen to twenty-eight days after discontinuing the dopamine infusion rats showed increased responsiveness to (–)NPA which persisted throughout the remainder of the 70-day withdrawal period. This long-term change was prevented when lithium was given continuously throughout the period of dopamine infusion, but not when lithium was given in divided doses, showing the importance of the mode of drug delivery. The long-term change caused by the dopamine infusion could also be prevented by bupropion but not by imipramine, amitriptyline or nomifensine to show again that the actions of classical antidepressant drugs may be differentiated from those of lithium and bupropion. Therefore, it is suggested that the model of phasic hyperactivity described may provide a means for more closely analysing, both behaviourally and biochemically, the site and mechanism of action of lithium (and bupropion) in the control of the short- and long-term consequences of an enhanced mesolimbic dopamine activity.Offprint requests: B. Costall