Lithium-induced gene expression of inducible cyclic adenosine monophosphate early repressor in the rat adrenal gland.
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 microg/5 microl) 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.
Spencer
Corinne M
CM
Program in Neuroscience, Florida State University, Tallahassee, Florida, USA.
Jahng
Jeong Won
JW
Ryu
Vitaly
V
Houpt
Thomas A
TA
D000302:Adrenal Cortex / Q000378:metabolism*; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology; D015415:Biomarkers; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D051786:Cyclic AMP Response Element Modulator / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D017781:Genes, Immediate-Early / Q000235:genetics; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D018692:Antimanic Agents; D015415:Biomarkers; C497412:Crem protein, rat; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D051786:Cyclic AMP Response Element Modulator; D003907:Dexamethasone; D000242:Cyclic AMP; D018021:Lithium Chloride; D003345:Corticosterone