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The Journal of Neuroscience, October 18, 2006, 26(42):10808-10812; doi:10.1523/JNEUROSCI.1661-06.2006

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Brief Communications
Blockade of Adenosine A_2A Receptors Prevents Protein Phosphorylation in the Striatum Induced by Cortical Stimulation

César Quiroz,¹ Catarina Gomes,² Arlene C. Pak,¹ Joaquim A. Ribeiro,² Steven R. Goldberg,¹ Bruce T. Hope,¹ and Sergi Ferré¹

¹Behavioral Neuroscience Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland 21224, and ²Institute of Pharmacology and Neurosciences, Faculty of Medicine, Institute of Molecular Medicine, University of Lisbon, 1649-028 Lisbon, Portugal

Correspondence should be addressed to Sergi Ferré, Preclinical Pharmacology Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Department of Health and Human Services, 5500 Nathan Shock Drive, Baltimore, MD 21224. Email: sferre{at}intra.nida.nih.gov

Previous studies have shown that cortical stimulation selectively activates extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and immediate early gene expression in striatal GABAergic enkephalinergic neurons. In the present study, we demonstrate that blockade of adenosine A_2A receptors with caffeine or a selective A_2A receptor antagonist counteracts the striatal activation of cAMP–protein kinase A cascade (phosphorylation of the Ser₈₄₅ residue of the glutamate receptor 1 subunit of the AMPA receptor) and mitogen-activated protein kinase (ERK1/2 phosphorylation) induced by the in vivo stimulation of corticostriatal afferents. The results indicate that A_2A receptors strongly modulate the efficacy of glutamatergic synapses on striatal enkephalinergic neurons.

Key words: caffeine; adenosine A_2A receptor; striatum; phosphorylation; ERK1/2; AMPA receptor

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Received April 18, 2006; revised Sept. 11, 2006; accepted Sept. 11, 2006.

Correspondence should be addressed to Sergi Ferré, Preclinical Pharmacology Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Department of Health and Human Services, 5500 Nathan Shock Drive, Baltimore, MD 21224. Email: sferre{at}intra.nida.nih.gov

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