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.
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Acknowledgments
This work was supported by Spanish MICINN (SAF 04/02784), MINECO (SAF2009-08460, SAF2013-48586-R), ERDF Funds and the Basque Government (IT-616-13).
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Animal care and all experimental protocols were performed in agreement with the European Ethical Standards (European Union Directive 2010/63/EU) and translation into Spanish legislation (RD 53/2013) and approved by the UPV/EHU Ethical Board for Animal Welfare (CEEA)
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Horrillo, I., Ortega, J.E., Diez-Alarcia, R. et al. Effect of subchronic corticosterone administration on α2-adrenoceptor functionality in rat brain: an in vivo and in vitro study. Psychopharmacology 233, 3861–3867 (2016). https://doi.org/10.1007/s00213-016-4418-3
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DOI: https://doi.org/10.1007/s00213-016-4418-3