Effect of lithium and lithium withdrawal on potassium-evoked dopamine release and tyrosine hydroxylase expression in the rat

The mood stabilizer lithium is used successfully in the treatment of bipolar affective disorder. However, treatment compliance is frequently poor and sudden withdrawal from lithium therapy is associated with a significantly increased risk of rebound mania. In this study we have used rodents to identify neurobiological changes in dopamine function occurring during chronic lithium treatment and withdrawal from chronic lithium treatment. Rats were maintained for 28d on a lithium diet or a control diet. A subgroup had their lithium diet substituted with a control diet from day 25 of the treatment period. In-vivo micro-dialysis was used to study both basal dopamine release and potassium-evoked dopamine released in the shell of the nucleus accumbens. In-situ hybridization histochemistry was used to study the abundance of mRNA coding for dopamine's synthetic enzyme, tyrosine hydroxylase in the ventral tegmental area. Basal dopamine levels did not differ across any of the three treatment groups. However, the potassium-evoked dopamine release was significantly attenuated in lithium and lithium-withdrawn rats compared to control rats. Tyrosine hydroxylase mRNA abundance in the ventral tegmental area did not differ between any of the three treatment groups. These data suggest that decreased dopamine release may mediate the mood stabilizing action of lithium. However, in this paradigm a rebound increase in dopamine release was not found after withdrawal from lithium treatment.