Constitutive Genetic Deletion of <i>Hcn1</i> Increases Alcohol Preference during Adolescence

The hyperpolarization-activated cyclic nucleotide-gated channel (HCN), which underlies the hyperpolarization-activated cation current (I<sub>h</sub>), has diverse roles in regulating neuronal excitability across cell types and brain regions. Recently, HCN channels have been implicated in...

Full description

Bibliographic Details
Main Authors: Michael C. Salling, Neil L. Harrison
Format: Article
Language:English
Published: MDPI AG 2020-10-01
Series:Brain Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3425/10/11/763
id doaj-e32ddf3c754241b58f8569c56028a6ed
record_format Article
spelling doaj-e32ddf3c754241b58f8569c56028a6ed2020-11-25T03:32:45ZengMDPI AGBrain Sciences2076-34252020-10-011076376310.3390/brainsci10110763Constitutive Genetic Deletion of <i>Hcn1</i> Increases Alcohol Preference during AdolescenceMichael C. Salling0Neil L. Harrison1Louisiana State University Health Sciences Center, New Orleans, LA 70112, USAColumbia University Irving Medical Center, New York, NY 10032, USAThe hyperpolarization-activated cyclic nucleotide-gated channel (HCN), which underlies the hyperpolarization-activated cation current (I<sub>h</sub>), has diverse roles in regulating neuronal excitability across cell types and brain regions. Recently, HCN channels have been implicated in preclinical models of substance abuse including alcohol. In the prefrontal cortex of rodents, HCN expression and I<sub>h</sub> magnitude are developmentally regulated during adolescence and may be vulnerable to alcohol’s effects. In mice, binge alcohol consumption during the adolescent period results in a sustained reduction in I<sub>h</sub> that coincides with increased alcohol consumption in adulthood, yet the direct role HCN channels have on alcohol consumption are unknown. Here, we show that the genetic deletion of <i>Hcn1</i> causes an increase in alcohol preference on intermittent 2-bottle choice task in homozygous null (HCN1<i><sup>−/−</sup></i>) male mice compared to wild-type littermates without affecting saccharine or quinine preference. The targeted viral deletion of HCN1 in pyramidal neurons of the medial prefrontal cortex resulted in a gradual loss of <i>Hcn1</i> expression and a reduction in I<sub>h</sub> magnitude during adolescence, however, this did not significantly affect alcohol consumption or preference. We conclude that while HCN1 regulates alcohol preference, the genetic deletion of <i>Hcn1</i> in the medial prefrontal cortex does not appear to be the locus for this effect.https://www.mdpi.com/2076-3425/10/11/763<i>Hcn1</i>alcoholprefrontal cortex
collection DOAJ
language English
format Article
sources DOAJ
author Michael C. Salling
Neil L. Harrison
spellingShingle Michael C. Salling
Neil L. Harrison
Constitutive Genetic Deletion of <i>Hcn1</i> Increases Alcohol Preference during Adolescence
Brain Sciences
<i>Hcn1</i>
alcohol
prefrontal cortex
author_facet Michael C. Salling
Neil L. Harrison
author_sort Michael C. Salling
title Constitutive Genetic Deletion of <i>Hcn1</i> Increases Alcohol Preference during Adolescence
title_short Constitutive Genetic Deletion of <i>Hcn1</i> Increases Alcohol Preference during Adolescence
title_full Constitutive Genetic Deletion of <i>Hcn1</i> Increases Alcohol Preference during Adolescence
title_fullStr Constitutive Genetic Deletion of <i>Hcn1</i> Increases Alcohol Preference during Adolescence
title_full_unstemmed Constitutive Genetic Deletion of <i>Hcn1</i> Increases Alcohol Preference during Adolescence
title_sort constitutive genetic deletion of <i>hcn1</i> increases alcohol preference during adolescence
publisher MDPI AG
series Brain Sciences
issn 2076-3425
publishDate 2020-10-01
description The hyperpolarization-activated cyclic nucleotide-gated channel (HCN), which underlies the hyperpolarization-activated cation current (I<sub>h</sub>), has diverse roles in regulating neuronal excitability across cell types and brain regions. Recently, HCN channels have been implicated in preclinical models of substance abuse including alcohol. In the prefrontal cortex of rodents, HCN expression and I<sub>h</sub> magnitude are developmentally regulated during adolescence and may be vulnerable to alcohol’s effects. In mice, binge alcohol consumption during the adolescent period results in a sustained reduction in I<sub>h</sub> that coincides with increased alcohol consumption in adulthood, yet the direct role HCN channels have on alcohol consumption are unknown. Here, we show that the genetic deletion of <i>Hcn1</i> causes an increase in alcohol preference on intermittent 2-bottle choice task in homozygous null (HCN1<i><sup>−/−</sup></i>) male mice compared to wild-type littermates without affecting saccharine or quinine preference. The targeted viral deletion of HCN1 in pyramidal neurons of the medial prefrontal cortex resulted in a gradual loss of <i>Hcn1</i> expression and a reduction in I<sub>h</sub> magnitude during adolescence, however, this did not significantly affect alcohol consumption or preference. We conclude that while HCN1 regulates alcohol preference, the genetic deletion of <i>Hcn1</i> in the medial prefrontal cortex does not appear to be the locus for this effect.
topic <i>Hcn1</i>
alcohol
prefrontal cortex
url https://www.mdpi.com/2076-3425/10/11/763
work_keys_str_mv AT michaelcsalling constitutivegeneticdeletionofihcn1iincreasesalcoholpreferenceduringadolescence
AT neillharrison constitutivegeneticdeletionofihcn1iincreasesalcoholpreferenceduringadolescence
_version_ 1724566247895465984