Identification and validation of midbrain Kcnq4 regulation of heavy alcohol consumption in rodents

Neuropharmacology
N S McGuierPatrick J Mulholland

Abstract

Currently available pharmacotherapies for treating alcohol use disorder (AUD) suffer from deleterious side effects and are not efficacious in diverse populations. Clinical and preclinical studies provide evidence that the Kcnq family of genes that encode KV7 channels influence alcohol intake and dependence. KV7 channels are a class of slowly activating voltage-dependent K+ channels that regulate neuronal excitability. Studies indicate that the KV7 channel positive modulator retigabine can decrease dopaminergic neuron firing, alter dopamine (DA) release, and reduce alcohol intake in heavy drinking rodents. Given the critical nature of ventral tegmental area (VTA) DA to the addiction process and predominant expression of Kcnq4 in DA neurons, we investigated the role of midbrain Kcnq genes and KV7 channels in the VTA of genetically diverse mice and long-term heavy drinking rats, respectively. Integrative bioinformatics analysis identified negative correlations between midbrain Kcnq4 expression and alcohol intake and seeking behaviors. Kcnq4 expression levels were also correlated with dopaminergic-related phenotypes in BXD strains, and Kcnq4 was present in support intervals for alcohol sensitivity and alcohol withdrawal severity QT...Continue Reading

Citations

Sep 27, 2018·The European Journal of Neuroscience·Carole MorelMing-Hu Han
Jan 2, 2021·Pharmacological Reports : PR·Ewa ZwierzyńskaBogusława Pietrzak
Jun 22, 2021·Frontiers in Molecular Neuroscience·Deepanjali Dwivedi, Upinder S Bhalla
Aug 13, 2021·Frontiers in Cellular Neuroscience·T BayasgalanB Pál

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