Lithium enhances 5-HT2A receptor-mediated c-fos expression in rat cerebral cortex.
The role of lithium in treating bipolar affective disorder is poorly understood; however, it may involve effects on brain 5-HT function. We have shown that the 5-HT2A/2C receptor agonist DOI (2,5-dimethoxy-4-iodophenylisopropylamine) induces the expression of c-fos in rat brain which correlates with the distribution of 5-HT2A receptors. We now report on the effect of lithium on 5-HT receptor activation. Rats were treated chronically with dietary lithium before being given either DOI or the 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin), and their brains were processed for c-fos immunohistochemistry. Lithium treatment greatly enhanced levels of Fos seen after DOI, but not after 8-OH-DPAT; layer II of caudal piriform cortex, previously devoid of staining, exhibited the most marked labelling. This suggests that chronic lithium selectively alters immediate-early gene expression in brain. Such alteration may underlie the action of lithium in treating bipolar affective disorder.
Leslie
R A
RA
Oxford University, SmithKline Beecham Centre for Applied Neuropsychobiology, UK.
Moorman
J M
JM
Grahame-Smith
D G
DG
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects*; D007150:Immunohistochemistry; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D000662:Amphetamines; D016760:Proto-Oncogene Proteins c-fos; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D008094:Lithium; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine