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Lithium-induced gene expression of inducible cyclic adenosine monophosphate early repressor in the rat adrenal gland

 Corinne M. Spencer  ;  Jeong Won Jahng  ;  Vitaly Ryu  ;  Thomas A. Houpt 
 JOURNAL OF NEUROSCIENCE RESEARCH, Vol.82(2) : 273-282, 2005 
Journal Title
Issue Date
Adrenal Cortex/metabolism* ; Animals ; Antimanic Agents/pharmacology ; Biomarkers ; Brain/drug effects* ; Brain/metabolism ; Corticosterone/metabolism ; Cyclic AMP/metabolism ; Cyclic AMP Response Element Modulator/genetics* ; Dexamethasone/pharmacology ; Dose-Response Relationship, Drug ; Gene Expression Regulation/drug effects ; Gene Expression Regulation/physiology ; Genes, Immediate-Early/genetics ; Hypothalamo-Hypophyseal System/drug effects* ; Hypothalamo-Hypophyseal System/metabolism ; Lithium Chloride/pharmacology* ; Male ; Pituitary-Adrenal System/drug effects* ; Pituitary-Adrenal System/metabolism ; Proto-Oncogene Proteins c-fos/genetics ; RNA, Messenger/drug effects ; RNA, Messenger/metabolism ; Rats ; Rats, Sprague-Dawley ; Time Factors ; Up-Regulation/drug effects ; Up-Regulation/physiology
hypothalamic‐pituitary‐adrenal gland axis ; dexamethasone ; c‐fos ; In situ hybridization
Lithium has acute and chronic effects on the hypothalamic-pituitary-adrenal gland (HPA) axis that are important for both therapeutic (e.g., treatment of mood disorders) and experimental (e.g., as the toxin in conditioned taste aversion studies) applications. We visualized lithium-induced activation of the HPA axis in rats by the adrenal expression of inducible cAMP early repressor (ICER), which is activated by elevated intracellular cAMP. We have shown that 1) intraperitoneal lithium chloride (LiCl) induces transient expression of ICER and c-fos mRNAs in the rat adrenal cortex and increases plasma level of corticosterone; 2) the cortical expression of ICER mRNA by LiCl occurs in a dose-dependent manner; 3) adrenal induction of ICER expression is delayed compared with c-fos expression; 4) dexamethasone pretreatment (4 mg/kg) blocks corticosterone release and adrenocortical ICER induction either by systemic LiCl (76 mg/kg) or by restraint stress; and 5) intracerebroventricular LiCl (127 μg/5 μl) is sufficient for adrenocortical, but not medullary, ICER induction. These results suggest that adrenocortical ICER expression could serve as a reliable marker for lithium-induced activation of the HPA axis. Understanding the activation of immediate-early genes such as c-fos or ICER in response to a single LiCl injection is an important first step in understanding the long-term changes in gene expression elicited by lithium that are involved in its therapeutic and toxic effect. The pattern and mechanism by which lithium stimulates ICER transcription in the adrenal gland would serve as a useful model system in future studies of lithium.
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1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Jahng, Jeong Won(장정원)
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