Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/33735

TitleAdenosine A(2A) receptor blockade reverts hippocampal stress-induced deficits and restores corticosterone circadian oscillation
Author(s)Batalha, V. L.
Pêgo, José M.
Fontinha, B. M.
Costenla, A. R.
Valadas, J. S.
Baqi, Y.
Radjainia, H.
Müller, C. E.
Sebastião, A. M.
Lopes, L. V.
KeywordsAdenosine A2A receptors
Corticosterone
Hippocampus
HPA-axis
Maternal separation
Stress
adenosine A receptors 2A
Issue date2013
PublisherNature Publishing Group
JournalMolecular Psychiatry
Abstract(s)Maternal separation (MS) is an early life stress model that induces permanent changes in the central nervous system, impairing hippocampal long-term potentiation (LTP) and spatial working memory. There are compelling evidences for a role of hippocampal adenosine A(2A) receptors in stress-induced modifications related to cognition, thus opening a potential window for therapeutic intervention. Here, we submitted rats to MS and evaluated the long-lasting molecular, electrophysiological and behavioral impairments in adulthood. We then assessed the therapeutic potential of KW6002, a blocker of A(2A) receptors, in stress-impaired animals. We report that the blockade of A(2A) receptors was efficient in reverting the behavior, electrophysiological and morphological impairments induced by MS. In addition, this effect is associated with restoration of the hypothalamic-pituitary-adrenal axis (HPA-axis) activity, as both the plasma corticosterone levels and hippocampal glucocorticoid receptor expression pattern returned to physiological-like status after the treatment. These results reveal the involvement of A(2A) receptors in the stress-associated impairments and directly in the stress response system by showing that the dysfunction of the HPA-axis as well as the long-lasting synaptic and behavioral effects of MS can be reverted by targeting adenosine A(2A) receptors. These findings provide a novel evidence for the use of adenosine A(2A) receptor antagonists as potential therapy against psychopathologies
TypeArticle
URIhttp://hdl.handle.net/1822/33735
DOI10.1038/mp.2012.8
ISSN1359-4184
Publisher versionhttp://www.nature.com/mp/journal/v18/n3/full/mp20128a.html
Peer-Reviewedyes
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

Files in This Item:
File Description SizeFormat 
batalha vl_mol psychiatry 2013 posp.pdf751 kBAdobe PDFView/Open

Partilhe no FacebookPartilhe no TwitterPartilhe no DeliciousPartilhe no LinkedInPartilhe no DiggAdicionar ao Google BookmarksPartilhe no MySpacePartilhe no Orkut
Exporte no formato BibTex mendeley Exporte no formato Endnote Adicione ao seu ORCID