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Title of Journal: J Mol Neurosci

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Abbravation: Journal of Molecular Neuroscience

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Springer US

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DOI

10.1007/s10357-004-0553-4

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1559-1166

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Cocaine Potentiates Multiple 5HTSubscript2A/Su

Authors: Jade M Franklin Gonzalo A Carrasco
Publish Date: 2014/09/12
Volume: 55, Issue: 3, Pages: 770-777
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Abstract

Cocaine addiction is a chronic relapsing disorder in which the underlying mechanisms are not well understood Here we used SpragueDawley rats injected with either saline 1 ml/kg or cocaine 15 mg/kg for 7 days bid ip to study the effect of cocaine on several components of 5HT2A receptor signaling in prefrontal cortex PFCx We detected enhanced activation of 5HT2A receptormediated phospholipase C beta PLCβ and extracellular regulated kinase 1/2 activity in PFCx of cocainetreated rats Although we were unable to detect changes in the protein levels of several proteins associated with 5HT2A receptor signaling such as caveolin1 postsynaptic density protein 95 βarrestin 2 etc we found a significant reduction in the phosphorylation status of cortical 5HT2A receptors This phenomenon was associated with reduced levels of Gprotein receptor kinase 5 GRK5 but not GRK2 or RSK2 proteins Our results suggest that decreased phosphorylation of 5HT2A receptors could mediate at least in part the cocaineinduced potentiation of multiple 5HT2A receptor signaling pathways in rat PFCx As discussed in this manuscript we hypothesize that preventing these neuroadaptations in 5HT2A receptor signaling may alleviate some of the aversive withdrawalassociated symptoms that contribute to relapse to cocaine abuse

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