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Effect of chronic lithium treatment on glucocorticoid and 5-HT1A receptor messenger RNA in hippocampal and dorsal raphe nucleus regions of the rat brain

Lookup NU author(s): Professor Richard McQuade, Mel LeitchORCiD, Dr Sasha Gartside, Professor Allan Young


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The therapeutic mechanism of action of lithium in the treatment of bipolar disorder is not well understood. Dysfunction of both 5-HT1A receptor mediated neurotransmission and the glucocorticoid receptor is associated with mood disorders, and preclinical studies suggest that lithium treatment can modulate these receptor subtypes. In this study, we investigated the effect of chronic lithium treatment on 5-HT1A receptors and glucocorticoid receptors in the rat brain. Male Sprague-Dawley rats were treated with lithium (3 mmol/kg/day) or saline for 28 days via subcutaneous implanted mini-osmotic pumps. After 28 days of treatment, the expression of mRNA for 5-HT1A receptors and glucocorticoid receptors in the rat hippocampus and dorsal raphe nucleus was determined by in situ hybridization histochemistry. Chronic administration of lithium decreased mRNA coding for post-synaptic 5-HT 1A receptors in hippocampal subregions but not for somatodentritic 5-HT1A receptors in the dorsal raphe nucleus. Chronic administration of lithium did not affect mRNA coding for glucocorticoid receptors in hippocampal subregions or in the dorsal raphe nucleus. Mean plasma lithium levels in the lithium-treated group were 0.50 ± 0.03 mmol/l; all animals appeared healthy and maintained a normal increase in body weight. Given recent reports implicating hypersensitive post-synaptic 5-HT1A receptors in bipolar manic patients, the present study suggests that down-regulation of this receptor population may be important in the therapeutic mechanism of action of lithium.

Publication metadata

Author(s): McQuade R, Leitch MM, Gartside SE, Young AH

Publication type: Article

Publication status: Published

Journal: Journal of Psychopharmacology

Year: 2004

Volume: 18

Issue: 4

Pages: 496-501

Print publication date: 01/12/2004

ISSN (print): 0269-8811

ISSN (electronic): 1461-7285

Publisher: Sage Publications Ltd.


DOI: 10.1177/0269881104047276

PubMed id: 15582915


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