Proceedings of The Physiological Society
University of Bristol (2005) J Physiol 567P, PC60
Urocortin 2 increases c-Fos expression in serotonergic neurons in the dorsal raphe nucleus.
Staub, Daniel; Spiga, Francesca; Lowry, Christopher A;
1. HWLINE, University of Bristol, Bristol, United Kingdom.
Corticotropin-releasing factor (CRF) is a 41-amino acid neuropeptide that is known to play a critical role in the regulation of stress-related behaviour and the hypothalamic-pituitary-adrenal (HPA) axis. The CRF family of neuropeptides also includes urocortin 1 (Ucn 1), urocortin 2 (Ucn 2), and urocortin 3 (Ucn 3). The role of these other CRF-related neuropeptides in the regulation of stress-related behaviour and the HPA axis activity is unclear. Ucn 2, acting on CRF2 receptors, may influence anxiety states through effects on brainstem neuromodulatory systems such as the serotonergic system. CRF2 receptor mRNA expression is abundant in the dorsal raphe nucleus (DR) suggesting that this may be an important site of action for Ucn 2 or other CRF2 receptor ligands (Day et al. 2004). To investigate the effects of CRF2 receptor activation on topographically organized subpopulations of serotonergic neurons in the DR and associated behavioural responses adult male Wistar rats were anaesthetized with 0.15 ml Hypnorm, (0.315 mg/ml fentanyl citrate and 10 mg/ml fluanisone; i.m.) and 0.15 ml diazepam (10 mg/2 ml i.p.) and fitted with a single I.C.V. guide cannula. One week following surgery rats received I.C.V. injections of vehicle, 0.01, 0.1, or 1.0 ug mouse Ucn 2 (mUcn 2). Home cage behaviours were recorded for 30 min prior to and 2 hours following drug treatment. Two hours following drug treatment, rats were anaesthetized with 0.5 ml Euthatal (200 mg/ml sodium pentobarbital), transcardially perfused with fixative, and brain tissues were processed for immunohistochemistry. mUcn 2 had no effect on most behavioural endpoints studied, however, mUcn 2 consistently increased c-Fos expression in subpopulations of serotonergic neurons identified by either tryptophan hydroxylase or serotonin immunostaining within topographically organized subdivisions of the DR, articularly the dorsal region of the middle and caudal DR (−7.64, −8.18, −8.54 and −9.16 mm bregma), regions that provide the majority of serotonergic innervation of stress-related or anxiety-related brain regions including the central nucleus of the amygdala (Abrams et al. 2004). With the exception of actions on drinking-related behaviour, the effects of mUcn 2 on c-Fos expression in serotonergic neurons within the DR were not associated with acute behavioural responses. mUcn 2 actions on serotonergic systems described here may contribute to delayed behavioural effects of Ucn 2 described previously, including orexigenic, locomotor, and anxiety-related effects in a variety of behavioural tests as well as potentiation of conditioned fear and induction of escape deficits in a model of learned helplessness.
Where applicable, experiments conform with Society ethical requirements