Effect of subchronic corticosterone administration on α2-adrenoceptor functionality in rat brain: an in vivo and in vitro study.
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.



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.



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.



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.
Department of Pharmacology, University of the Basque Country (UPV/EHU), E-48940, Leioa, Bizkaia, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Leioa, Spain.|BioCruces Health Research Institute, Barakaldo, Spain.
Igor
I
Horrillo
Department of Pharmacology, University of the Basque Country (UPV/EHU), E-48940, Leioa, Bizkaia, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Leioa, Spain.|BioCruces Health Research Institute, Barakaldo, Spain.
Jorge E
JE
Ortega
Department of Pharmacology, University of the Basque Country (UPV/EHU), E-48940, Leioa, Bizkaia, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Leioa, Spain.|BioCruces Health Research Institute, Barakaldo, Spain.
Rebeca
R
Diez-Alarcia
Department of Pharmacology, University of the Basque Country (UPV/EHU), E-48940, Leioa, Bizkaia, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Leioa, Spain.|BioCruces Health Research Institute, Barakaldo, Spain.
Leyre
L
Urigüen
Department of Pharmacology, University of the Basque Country (UPV/EHU), E-48940, Leioa, Bizkaia, Spain. javier.meana@ehu.eus.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Leioa, Spain. javier.meana@ehu.eus.|BioCruces Health Research Institute, Barakaldo, Spain. javier.meana@ehu.eus.
J Javier
JJ
Meana
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology*; D004195:Disease Models, Animal; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008125:Locus Coeruleus / Q000187:drug effects; D008297:Male; D017551:Microdialysis; D009638:Norepinephrine / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D011941:Receptors, Adrenergic; D003000:Clonidine; D003345:Corticosterone; D009638:Norepinephrine
Adrenoceptor; Corticosterone; Depression; HPA; Mood disorders