Uptake of lithium into rat brain after acute and chronic administration

Abstract

Lithium is licensed for the treatment of bipolar disorders and also discussed in relation to neuroprotective properties. Although the drug has a small therapeutic window, its uptake and passage into the brain are poorly understood. We administered lithium to rats, following an acute (3mmol/kg, i.p.) or chronic (3mmol/kg/day, p.o.) regime. Lithium levels were assessed in serum, brain homogenate, cerebrospinal fluid (CSF) and, by means of microdialysis, in the extracellular space (ECS) of the brain 2, 6 and 24h post injection or after 3 weeks of chronic administration. Lithium is detected in brain ECS within minutes of administration and reaches maximum levels in brain extracellular fluid after 30min. In the early phase after lithium administration (2 and 6h), serum levels of lithium do not differ significantly from those assessed in CSF and brain homogenate. Afterwards, however, accumulation in brain tissue occurs. As a consequence, after 24h and 3 weeks, lithium levels in brain homogenate (i.e., intracellular levels) are significantly higher than in CSF or dialysates (i.e., extracellular levels). In conclusion, lithium rapidly reaches the brain, but after prolonged treatment, brain intracellular levels are high and poorly represented by plasma or CSF measurements.