Adenosine A2A receptor blockade reverts hippocampal stress-induced deficits and restores corticosterone circadian oscillation

V. L. Batalha, J. M. Pego, B. M. Fontinha, A. R. Costenla, J. S. Valadas, Y. Baqi, H. Radjainia, C. E. Müller, A. M. Sebastião, L. V. Lopes

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

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 A2A 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 A2A receptors, in stress-impaired animals. We report that the blockade of A2A 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 A2A 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 A2A receptors. These findings provide a novel evidence for the use of adenosine A2A receptor antagonists as potential therapy against psychopathologies.

Original languageEnglish
Pages (from-to)320-331
Number of pages12
JournalMolecular Psychiatry
Volume18
Issue number3
DOIs
Publication statusPublished - Mar 2013

Fingerprint

Adenosine A2A Receptors
Corticosterone
Mothers
Adenosine A2 Receptor Antagonists
Long-Term Potentiation
Glucocorticoid Receptors
Therapeutics
Psychopathology
Short-Term Memory
Psychological Stress
Cognition
Central Nervous System

Keywords

  • adenosine A receptors
  • corticosterone
  • hippocampus
  • HPA-axis
  • maternal separation
  • stress

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Adenosine A2A receptor blockade reverts hippocampal stress-induced deficits and restores corticosterone circadian oscillation. / Batalha, V. L.; Pego, J. M.; Fontinha, B. M.; Costenla, A. R.; Valadas, J. S.; Baqi, Y.; Radjainia, H.; Müller, C. E.; Sebastião, A. M.; Lopes, L. V.

In: Molecular Psychiatry, Vol. 18, No. 3, 03.2013, p. 320-331.

Research output: Contribution to journalArticle

Batalha, VL, Pego, JM, Fontinha, BM, Costenla, AR, Valadas, JS, Baqi, Y, Radjainia, H, Müller, CE, Sebastião, AM & Lopes, LV 2013, 'Adenosine A2A receptor blockade reverts hippocampal stress-induced deficits and restores corticosterone circadian oscillation', Molecular Psychiatry, vol. 18, no. 3, pp. 320-331. https://doi.org/10.1038/mp.2012.8
Batalha, V. L. ; Pego, J. M. ; Fontinha, B. M. ; Costenla, A. R. ; Valadas, J. S. ; Baqi, Y. ; Radjainia, H. ; Müller, C. E. ; Sebastião, A. M. ; Lopes, L. V. / Adenosine A2A receptor blockade reverts hippocampal stress-induced deficits and restores corticosterone circadian oscillation. In: Molecular Psychiatry. 2013 ; Vol. 18, No. 3. pp. 320-331.
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