RT Journal Article SR Electronic T1 cAMP Response Element-Mediated Gene Transcription Is Upregulated by Chronic Antidepressant Treatment JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 4030 OP 4036 DO 10.1523/JNEUROSCI.20-11-04030.2000 VO 20 IS 11 A1 J. Thome A1 N. Sakai A1 K.-H. Shin A1 C. Steffen A1 Y.-J. Zhang A1 S. Impey A1 D. Storm A1 R. S. Duman YR 2000 UL http://www.jneurosci.org/content/20/11/4030.abstract AB Regulation of gene transcription via the cAMP-mediated second messenger pathway has been implicated in the actions of antidepressant drugs, but studies to date have not demonstrated such an effectin vivo. To directly study the regulation of cAMP response element (CRE)-mediated gene transcription by antidepressants, transgenic mice with a CRE–LacZ reporter gene construct were administered one of three different classes of antidepressants: a norepinephrine selective reuptake inhibitor (desipramine), a serotonin selective reuptake inhibitor (fluoxetine), or a monoamine oxidase inhibitor (tranylcypromine). Chronic, but not acute, administration of these antidepressants significantly increased CRE-mediated gene transcription, as well as the phosphorylation of CRE binding protein (CREB), in several limbic brain regions thought to mediate the action of antidepressants, including the cerebral cortex, hippocampus, amygdala, and hypothalamus. These results demonstrate that chronic antidepressant treatment induces CRE-mediated gene expression in a neuroanatomically differentiated pattern and further elucidate the molecular mechanisms underlying the actions of these widely used therapeutic agents.