Effects of acute and chronic lithium treatment on amphetamine-induced dopamine increase in the nucleus accumbens and prefrontal cortex in rats as studied by microdialysis.

The effects of acute and chronic administration of lithium (Li) on the basal levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxy-indoleacetic acid (5-HIAA), and the amphetamine-induced DA increase were assessed in the Nucleus Accumbens (NAC) and Prefrontal Cortex (PFC) by brain dialysis in freely-moving rats. Acute Li (2 meq/L) was locally administered by reverse dialysis. Chronic Li (2 meq/kg) was intragastrically administered for 14 days. No effect was observed after acute Li administration. However, after chronic Li administration, the basal levels of DOPAC and the amphetamine-induced DA increase in the NAC were significantly higher in the Li-treated rats than in the saline-treated controls. In the PFC, while the amphetamine-induced DA increase was not affected by chronic Li, the basal levels of DA and DOPAC were significantly decreased after Li administration. The effects of chronic Li in the NAC could be due to increased synthesis and/or decreased release of DA, whereas in the PFC the effects could be due to a decreased synthesis of DA. The absence of effects of acute Li administration is in agreement with the therapeutic inefficacy of the acute use of the cation. The changes observed after chronic treatment in the NAC and the PFC could be related to the effects of Li on mood disorders and cognitive functions, respectively.