Cocaine sensitization inhibits the hyperpolarization-activated cation current Ih and reduces cell size in dopamine neurons of the ventral tegmental area.
Enviado por Francisco Mariano Arencibia-Albi... el
Título | Cocaine sensitization inhibits the hyperpolarization-activated cation current Ih and reduces cell size in dopamine neurons of the ventral tegmental area. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Autores | Arencibia-Albite, F, Vázquez, R, Velásquez-Martinez, MC, Jiménez-Rivera, CA |
Journal | J Neurophysiol |
Volume | 107 |
Issue | 8 |
Pagination | 2271-82 |
Date Published | 2012 Apr |
ISSN | 1522-1598 |
Palabras clave | Animals, Cell Size, Cocaine, Cyclic Nucleotide-Gated Cation Channels, Dopaminergic Neurons, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Male, Motor Activity, Neural Inhibition, Potassium Channels, Rats, Rats, Sprague-Dawley, Ventral Tegmental Area |
Abstract | The progressive augmentation of motor activity that results from repeated cocaine administration is termed behavioral sensitization. This phenomenon is thought to be a critical component in compulsive drug taking and relapse. Still, the cellular mechanisms that underlie sensitization remain elusive. Cocaine abuse, nonetheless, is known to evoke neuroplastic adaptations in dopamine (DA) neurotransmission originating from the midbrain's ventral tegmental area (VTA). Here, we report that concomitant with the development of locomotor sensitization to cocaine the hyperpolarization-activated cation current (I(h)) amplitude is depressed by ∼40% in VTA DA cells. Such effect did not result from a negative shift in I(h) voltage dependence. Nonstationary fluctuation analysis indicates that this inhibition was caused by an ∼45% reduction in the number of h-channels with no change in their unitary properties. The cocaine-induced I(h) depression was accompanied by a reduction in cell capacitance of similar magnitude (∼33%), leaving h-current density unaltered. Two implications follow from these data. First, I(h) inhibition may contribute to cocaine addiction by increasing bursting probability in DA cells and this effect could be intensified by the decrease in cell capacitance. Second, the cocaine-induced diminution of DA cell capacitance may also lead to reward tolerance promoting drug-seeking behaviors. |
DOI | 10.1152/jn.00818.2011 |
Alternate Journal | J. Neurophysiol. |
PubMed ID | 22262829 |
PubMed Central ID | PMC3331609 |
Grant List | GM-08224 / GM / NIGMS NIH HHS / United States GM-084854 / GM / NIGMS NIH HHS / United States S06 GM050695 / GM / NIGMS NIH HHS / United States SC1 GM084854 / GM / NIGMS NIH HHS / United States |