Chronic lithium treatment decreases neuronal activity in the nucleus accumbens and cingulate cortex of the rat

Although the efficacy of lithium as a mood stabilizer is well documented, t he mechanism of its therapeutic effect associated with prolonged treatment remains unknown. Identifying discrete brain regions and neural pathways tha t are functionally altered following long-term lithium treatment is central to elucidating a psychotherapeutic mechanism. We have used a sensitive and quantitative histochemical assay for the determination of cytochrome oxida se (CO) activity, a mitochondrial marker of neuronal activity, to determine the effcect of repeated lithium treatment on regional neuronal activity in the mt brain. Oral lithium treatment (21 days) selectively decreased cytoc hrome oxidase activity in the cingulate cortex and regions of the nucleus a ccumbens. These decreases were not seen after 5 days of lithium administrat ion, although serum lithium concentrations were similar after both 5 and 21 days of treatment. The analysis of interregional correlations further sugg ests a role for amygdala pathways in the effects of lithium following 21 da ys of treatment. The implications of these data for understanding the mecha nisms of action of lithium are discussed. (C) 1999 American College of Neur opsychopharmacology. Published by Elsevier Science Inc.