title: Comparison of alterations in c-fos and Egr-1 (zif268) expression throughout the rat brain following acute administration of different classes of antidepressant compounds.
abstract: The majority of immediate-early gene (IEG) studies focus on a few key brain regions associated with the class of psychoactive compound being studied. Recently, using a meta-analysis of the c-fos literature, we demonstrated the utility of c-fos profiling to classify such compounds. The present study examined acute delivery of a range of antidepressant classes; fluoxetine, imipramine, LiCl, and mirtazapine. The dual aims were to study the IEG profiles of these varying classes of antidepressants throughout the rat brain and to compare the utility of c-fos or Egr-1 as IEGs to classify clinically efficacious antidepressants. All antidepressants increased c-fos mRNA in the central amygdala, as previously shown, while c-fos was also increased in the anterior insular cortex and significantly decreased within the septum. Although acute antidepressant administration altered c-fos expression in a number of brain regions, Egr-1 expression was only significantly altered in the central amygdala, suggesting that Egr-1 may not be as useful a marker to investigate acute antidepressant treatment. The fact that these drugs, including the previously unclassified antidepressant mirtazapine, share a number of common loci of activation, which are implicated by human and animal studies in depression, adds further support to the use of IEG mapping to classify psychoactive compounds.
authors.affiliation: Psychopharmacology Unit, Dorothy Hodgkin Building, Whitson Street, University of Bristol, Bristol, UK. david_anthony.slattery@novartis.com
authors.forename: David A
authors.initials: DA
authors.lastname: Slattery
authors.forename: John A
authors.initials: JA
authors.lastname: Morrow
authors.forename: Alan L
authors.initials: AL
authors.lastname: Hudson
authors.forename: David R
authors.initials: DR
authors.lastname: Hill
authors.forename: David J
authors.initials: DJ
authors.lastname: Nutt
authors.forename: Brian
authors.initials: B
authors.lastname: Henry
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001345:Autoradiography / Q000379:methods; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects*; D004277:DNA, Single-Stranded / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000928:Antidepressive Agents; C400152:DNA enzyme ED5; D004277:DNA, Single-Stranded; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D000110:Acetylcholinesterase