Dynamics of c-fos and ICER mRNA expression in rat forebrain following lithium chloride injection

Lithium is commonly used as a treatment for affective disorders in humans a nd as a toxin to produce conditioned taste aversions in rats. LiCl administ ration in rats has been correlated with activation of c-fos and cAMP-mediat ed gene transcription in many brain regions; however, little is known about the timing or duration of gene activation. We hypothesized that c-fos gene transcription is rapidly stimulated by LiCl, followed later by the express ion of the inducible cAMP early repressor (ICER) transcription factor, a ne gative modulator of CAMP-mediated gene transcription. By in situ hybridizat ion, we analyzed the timecourse of c-fos and ICER mRNA expression in the ce ntral nucleus of the amygdala (CeA), the paraventricular nucleus of the hyp othalamus (PVN) and the supraoptic nucleus (SON) at seven time points (0, 0 .3, 1, 3, 6, 9 and 12 h) after intraperitoneal LiCl injection (0.15 M, 12 m l/kg, 76 mg/kg). Expression of c-fos mRNA peaked between 20 min and 1 h and returned to baseline by 3 h in the CeA, PVN and SON. ICER mRNA was detecte d in these regions at 20 min, peaked at 1-3 h and returned to nearly baseli ne 9 h following LiCl injection. The time lag between c-fos mRNA expression and ICER mRNA expression within the same regions is consistent with ICER t erminating c-fos gene transcription. However, no refractory period was dete cted for restimulation of c-fos transcription by a second injection of LiCl during the period of peak ICER mRNA expression, suggesting the involvement of other transcriptional modulators. (C) 2001 Elsevier Science BY. All rig hts reserved.