title: Urocortin 2 increases c-Fos expression in topographically organized subpopulations of serotonergic neurons in the rat dorsal raphe nucleus.
abstract: Corticotropin-releasing factor (CRF)-related peptides modulate stress-related physiology and behavior. Some of the physiological and behavioral effects of CRF-related peptides may be due to actions on CRF type 2 (CRF2) receptors modulating serotonergic systems in the dorsal raphe nucleus (DR). To determine if CRF2 receptor activation has effects on serotonergic neurons in the DR in conscious behaving rats, we gave intracerebroventricular (icv) injections of the selective CRF2 receptor agonist urocortin 2 (0, 0.01, 0.1, or 1.0 mug in 2 microl saline) to adult male Wistar rats and quantified c-Fos expression in topographically organized subpopulations of serotonergic neurons within the DR. In addition, home cage behaviors were recorded for 30 min prior to drug treatment and for 2 h following drug treatment. Two hours following drug treatment, rats were anesthetized, transcardially perfused with fixative, and brain tissues were processed for immunohistochemistry. Urocortin 2, in the absence of any effects on most behavioral endpoints studied, consistently increased c-Fos expression in subpopulations of serotonergic neurons identified by either tryptophan hydroxylase or serotonin immunostaining within specific subdivisions of the DR, particularly the dorsal region of the mid-rostrocaudal and caudal DR (-7.64, -8.18, -8.54, and -9.16 mm bregma). These studies demonstrate that urocortin 2 has selective actions on a subset of DR serotonergic neurons. Urocortin 2 actions on serotonergic systems described here may contribute to delayed behavioral effects of urocortin 2 described previously, including orexigenic, locomotor, and anxiety-related effects in a variety of behavioral tests as well as potentiation of conditioned fear and induction of escape deficits in a model of learned helplessness.
authors.affiliation: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK. d.staub@bristol.ac.uk
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Staub
authors.forename: Francesca
authors.initials: F
authors.lastname: Spiga
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lowry
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001931:Brain Mapping; D002452:Cell Count; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D005786:Gene Expression Regulation / Q000187:drug effects*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009474:Neurons / Q000145:classification / Q000187:drug effects* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D011897:Random Allocation; D011903:Raphe Nuclei / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D054832:Urocortins
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D054832:Urocortins; D012701:Serotonin; D003346:Corticotropin-Releasing Hormone; D014365:Tryptophan Hydroxylase