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Effects of lithium on the dopamine D2 receptor expression in the rat brain striatum were studied. Feeding the chow containing 0.2% LiCO3 for 6 days increased the level of the dopamine D2 receptor mRNA, and the transcription rate of the dopamine D2 receptor gene, indicating the stimulatory effects of lithium on the transcription of the dopamine D2 receptor gene. [3H] Spiperone binding to the striatal membranes increased in the rats treated with lithium, while the Western blotting analysis showed no change of the amount of the dopamine D2 receptors. These results suggested that lithium might induce the conformational changes of the dopamine D2 receptors. The methamphetamine-induced locomotor activity was enhanced by the pretreatment with lithium, whereas simultaneous increase in the methamphetamine concentration in the striatum was also observed. These observations suggested that the stimulation of methamphetamine-induced locomotor activity by lithium might be, at least partly, due to either increased sensitivity of the dopamine receptors, or increased concentration of methamphetamine in brain, or combination of both.