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Blockade of adenosine A2A receptors prevents protein phosphorylation in the striatum induced by cortical stimulation

César Quiroz1, Catarina Gomes, Arlene C Pak

  • 1Behavioral Neuroscience Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland 21224, USA.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|October 20, 2006
PubMed

Insights

Adenosine A2A receptors modulate glutamatergic synapses in the striatum. Blocking these receptors with caffeine or antagonists counteracts key signaling pathways activated by cortical stimulation in enkephalinergic neurons.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Cortical stimulation activates specific signaling pathways in striatal GABAergic enkephalinergic neurons.
  • Extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and immediate early gene expression are key markers of this activation.

Purpose of the Study:

  • To investigate the role of adenosine A2A receptors in modulating signaling pathways within striatal enkephalinergic neurons during corticostriatal stimulation.
  • To determine if blocking adenosine A2A receptors affects the activation of cAMP-protein kinase A and mitogen-activated protein kinase cascades.

Main Methods:

  • In vivo stimulation of corticostriatal afferents in rodent models.
  • Administration of caffeine or a selective adenosine A2A receptor antagonist.
  • Assessment of signaling pathway activation, including ERK1/2 phosphorylation and AMPA receptor subunit phosphorylation.

Main Results:

  • Blockade of adenosine A2A receptors counteracted the activation of the cAMP-protein kinase A cascade (Ser845 phosphorylation of GluR1 subunit of AMPA receptor).
  • Adenosine A2A receptor blockade also inhibited mitogen-activated protein kinase (ERK1/2 phosphorylation) activation induced by corticostriatal stimulation.
  • These findings highlight the significant role of A2A receptors in regulating synaptic efficacy.

Conclusions:

  • Adenosine A2A receptors play a crucial role in modulating the efficacy of glutamatergic synapses on striatal enkephalinergic neurons.
  • Targeting adenosine A2A receptors may represent a therapeutic strategy for conditions involving altered striatal function.

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