Cocaine Sensitization Increases I h Current Channel Subunit 2 (HCN 2 ) Protein Expression in Structures of the Mesocorti
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Cocaine Sensitization Increases Ih Current Channel Subunit 2 (HCN2) Protein Expression in Structures of the Mesocorticolimbic System Bermary Santos-Vera & Rafael Vázquez-Torres & Hermes G. García Marrero & Juan M. Ramos Acevedo & Francisco Arencibia-Albite & María E. Vélez-Hernández & Jorge D. Miranda & Carlos A. Jiménez-Rivera
Received: 7 August 2012 / Accepted: 5 November 2012 / Published online: 1 December 2012 # Springer Science+Business Media New York 2012
Abstract Alteration of the biological activity among neuronal components of the mesocorticolimbic (MCL) system has been implicated in the pathophysiology of drug abuse. Changes in the electrophysiological properties of neurons involved in the reward circuit seem to be of utmost importance in addiction. The hyperpolarization-activated cyclic nucleotide current, Ih, is a prominent mixed cation current present in neurons. The biophysical properties of the Ih and its potential modulatory role in cell excitability depend on the expression profile of the hyperpolarization-activated cyclic nucleotide gated channel (HCN) subunits. We investigated whether cocaine-induced behavioral sensitization, an animal model of drug addiction, elicits region-specific changes in the expression of the HCN2 channel’s subunit in the MCL system. Tissue samples from the ventral tegmental area, prefrontal cortex, nucleus accumbens, and hippocampus were analyzed using Western blot. Our findings demonstrate that cocaine treatment induced a significant increase in the expression profile of the HCN2 subunit in both its glycosylated and non-glycosylated protein isoforms in all areas tested. The increase in the glycosylated isoform was only observed in the ventral tegmental area. Together, these data suggest that
Jorge D. Miranda and Carlos A. Jiménez-Rivera contributed equally to this work. B. Santos-Vera : R. Vázquez-Torres : F. Arencibia-Albite : M. E. Vélez-Hernández : J. D. Miranda : C. A. Jiménez-Rivera (*) Department of Physiology and Biophysics, University of Puerto Rico School of Medicine, Medical Sciences Campus, PO Box 365067, 00936-5067, San Juan, Puerto Rico e-mail: [email protected] H. G. G. Marrero : J. M. R. Acevedo Department of Neurosurgery, University of Puerto Rico School of Medicine, 00936-5067, San Juan, Puerto Rico
the observed changes in MCL excitability during cocaine addiction might be associated with alterations in the subunit composition of their HCN channels. Keywords Addiction . Cocaine sensitization . Ventral tegmental area . Accumbens . Ih current . HCN channels
Introduction Neuroadaptations within the mesocorticolimbic (MCL) system are hypothesized to trigger drug addiction (Kauer 2003; Chen et al. 2010). Cocaine blocks cell membrane transporters that usually remove monoamines from the synaptic cleft once these neurotransmitters are released (Reith et al. 1997). This blockade produces a fast elevation of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) levels that, with chronic administration, results in an enduring psychomotor stimulation (So
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