Igor Horrillo1,2,3, Jorge E Ortega1,2,3, Rebeca Diez-Alarcia1,2,3, Leyre Urigüen1,2,3, J Javier Meana4,5,6. 1. Department of Pharmacology, University of the Basque Country (UPV/EHU), E-48940, Leioa, Bizkaia, Spain. 2. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Leioa, Spain. 3. BioCruces Health Research Institute, Barakaldo, Spain. 4. Department of Pharmacology, University of the Basque Country (UPV/EHU), E-48940, Leioa, Bizkaia, Spain. javier.meana@ehu.eus. 5. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Leioa, Spain. javier.meana@ehu.eus. 6. BioCruces Health Research Institute, Barakaldo, Spain. javier.meana@ehu.eus.
Abstract
RATIONALE: Noradrenergic system plays a critical role in the hypothalamic-pituitary-adrenal (HPA) axis regulation and the stress response. A dysregulated HPA axis may be indicative of an increased biological vulnerability for depression. In addition, a variety of studies have focused on specific alterations of α2-adrenoceptors as a mechanism involved in the pathogenesis of mood disorders and antidepressant response. OBJECTIVES: This study aimed to evaluate the effect of subchronic corticosterone administration on rat brain α2-adrenoceptor functionality by in vitro [35S]GTPγS binding stimulation assays and in vivo dual-probe microdialysis determination of extracellular noradrenaline concentrations. RESULTS: Implantation of a time release corticosterone pellet during 14 days induced sustained changes in endocrine function. However, there were no differences in α2-adrenoceptor agonist UK14304-induced stimulation of [35S]GTPγS binding in prefrontal cortex (PFC) between corticosterone-treated and control rats. In the same way, the in vivo evaluation of α2-adrenoceptor-mediated noradrenaline release responses to the α2-adrenoceptor agonist clonidine local administration into the locus coeruleus (LC), and the PFC did not show differences between the groups. CONCLUSIONS: The present results show that subchronic corticosterone administration does not induce changes on functionality of α2-adrenoceptors neither in the LC nor in noradrenergic cortical terminal areas.
RATIONALE: Noradrenergic system plays a critical role in the hypothalamic-pituitary-adrenal (HPA) axis regulation and the stress response. A dysregulated HPA axis may be indicative of an increased biological vulnerability for depression. In addition, a variety of studies have focused on specific alterations of α2-adrenoceptors as a mechanism involved in the pathogenesis of mood disorders and antidepressant response. OBJECTIVES: This study aimed to evaluate the effect of subchronic corticosterone administration on rat brain α2-adrenoceptor functionality by in vitro [35S]GTPγS binding stimulation assays and in vivo dual-probe microdialysis determination of extracellular noradrenaline concentrations. RESULTS: Implantation of a time release corticosterone pellet during 14 days induced sustained changes in endocrine function. However, there were no differences in α2-adrenoceptor agonist UK14304-induced stimulation of [35S]GTPγS binding in prefrontal cortex (PFC) between corticosterone-treated and control rats. In the same way, the in vivo evaluation of α2-adrenoceptor-mediated noradrenaline release responses to the α2-adrenoceptor agonist clonidine local administration into the locus coeruleus (LC), and the PFC did not show differences between the groups. CONCLUSIONS: The present results show that subchronic corticosterone administration does not induce changes on functionality of α2-adrenoceptors neither in the LC nor in noradrenergic cortical terminal areas.
Authors: Melville M Leitch; Colin D Ingram; Allan H Young; Richard McQuade; Sarah E Gartside Journal: Neuropsychopharmacology Date: 2003-01 Impact factor: 7.853