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Original Article |
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Neuropsychopharmacology (1999) 21 229-237.10.1038/sj.npp.1395300
Chronic Lithium Treatment Decreases Neuronal Activity in the Nucleus Accumbens and Cingulate Cortex of the Rat
Philip D Lambert1 Ph.D, Kathleen M McGirr2 BS, Timothy D Ely3 BA, Clinton D Kilts3 Ph.D and Michael J Kuhar2 Ph.D |
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1Regeneron Pharmaceuticals, Inc., Tarrytown, New York
2Yerkes Regional Primate Research Center, Emory University, Atlanta, Georgia
3Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, USA
Correspondence: Dr Philip D Lambert, Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591
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ABSTRACT
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Although the efficacy of lithium as a mood stabilizer is well documented, the mechanism of its therapeutic effect associated with prolonged treatment remains unknown. Identifying discrete brain regions and neural pathways that 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 oxidase (CO) activity, a mitochondrial marker of neuronal activity, to determine the effect of repeated lithium treatment on regional neuronal activity in the rat brain. Oral lithium treatment (21 days) selectively decreased cytochrome oxidase activity in the cingulate cortex and regions of the nucleus accumbens. These decreases were not seen after 5 days of lithium administration, although serum lithium concentrations were similar after both 5 and 21 days of treatment. The analysis of interregional correlations further suggests a role for amygdala pathways in the effects of lithium following 21 days of treatment. The implications of these data for understanding the mechanisms of action of lithium are discussed.
Keywords: Lithium; Cytochrome oxidase; Cingulate cortex; Nucleus accumbens; Amygdala; Imaging; Bipolar disorder |
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