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...
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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 |
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