title: Cocaine sensitization increases I h current channel subunit 2 (HCN₂) protein expression in structures of the mesocorticolimbic system.
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, I h, is a prominent mixed cation current present in neurons. The biophysical properties of the I h 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 the observed changes in MCL excitability during cocaine addiction might be associated with alterations in the subunit composition of their HCN channels.
authors.affiliation: Department of Physiology and Biophysics, University of Puerto Rico School of Medicine, Medical Sciences Campus, PO Box 365067, 00936-5067, San Juan, Puerto Rico.
authors.forename: Bermary
authors.initials: B
authors.lastname: Santos-Vera
authors.forename: Rafael
authors.initials: R
authors.lastname: Vázquez-Torres
authors.forename: Hermes G García
authors.initials: HG
authors.lastname: Marrero
authors.forename: Juan M Ramos
authors.initials: JM
authors.lastname: Acevedo
authors.forename: Francisco
authors.initials: F
authors.lastname: Arencibia-Albite
authors.forename: María E
authors.initials: ME
authors.lastname: Vélez-Hernández
authors.forename: Jorge D
authors.initials: JD
authors.lastname: Miranda
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Jiménez-Rivera
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D020033:Protein Isoforms; D003042:Cocaine