title: Altered regulation of CREB by chronic antidepressant administration in the brain of transgenic mice with impaired glucocorticoid receptor function.
abstract: Various effects of antidepressant drugs on gene transcription have been described and altered gene expression has been proposed as being a common biological basis underlying depressive illness. One target for the common action of antidepressants is a modifying effect on the regulation of postreceptor pathways and genes related to the cAMP cascade. Recent studies have demonstrated that long-term antidepressant treatment resulted in sustained activation of the cyclic adenosine 3',5'-monophosphate system and in increased expression of the transcription factor cAMP response element binding protein (CREB). A transgenic animal model of depression with impaired glucocorticoid receptor function was used to investigate the effect of chronic antidepressant treatments on CREB expression in different brain areas. Wild-type and transgenic mice received one administration of saline, desipramine, or fluoxetine, daily for 21 days. The effects of antidepressants on CREB mRNA were analyzed using a sensitive RNase protection assay. Antidepressant treatment resulted in a neuroanatomically and animal specific expression pattern of CREB. Our findings suggest that life-long central glucocorticoid receptor dysfunction results in an altered sensitivity with respect to the effects of antidepressants on the expression of CREB.
authors.affiliation: Department of Psychology, Università Vità-Salute San Raffaele, Via Olgettina 58, Milan, Italy. blom@mailserver.unimi.it
authors.forename: Joan M C
authors.initials: JM
authors.lastname: Blom
authors.forename: Fabio
authors.initials: F
authors.lastname: Tascedda
authors.forename: Serena
authors.initials: S
authors.lastname: Carra
authors.forename: Chiara
authors.initials: C
authors.lastname: Ferraguti
authors.forename: Nicholas
authors.initials: N
authors.lastname: Barden
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Brunello
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007274:Injections, Intraperitoneal; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D011965:Receptors, Glucocorticoid / Q000172:deficiency* / Q000235:genetics*
chemical_list: D000928:Antidepressive Agents; D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid