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No evidence of a role of the β 4 subunit of the nicotinic acetylcholine receptor in alcohol-related behaviors

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ABSTRACT

Background: Nicotinic acetylcholine receptors have gained attention in the last several years as mediators of alcohol-related behaviors. The genes that code for the α5, α3, and β4 subunits (Chrna5, Chrna3, and Chrnb4, respectively) map adjacent to each other on human chromosome 15/mouse chromosome 9. Genetic variants in this region have been associated with alcohol phenotypes and mice that overexpress these three subunits have reduced ethanol intake. In the present experiments, we examined the role of the Chrnb4 gene in three ethanol behaviors: consumption, ataxia, and sedation. Wildtype, heterozygous, and knockout mice were tested for ethanol consumption with a 2-bottle choice procedure and the drinking-in-the-dark paradigm. Ethanol-induced ataxia was measured with the balance beam and dowel test. Finally, the sedative effects of ethanol were measured with the loss of righting reflex paradigm.

Results: We observed no significant genotypic effects on any of the ethanol behaviors examined, suggesting that the β4 subunit is not involved in mediating these responses.

Conclusions: While we found no evidence for the involvement of the β4 subunit in ethanol responses, it is possible that this subunit modulates other behaviors not tested and further work should address this before completely ruling out its involvement.

Electronic supplementary material: The online version of this article (doi:10.1186/s13104-017-2470-7) contains supplementary material, which is available to authorized users.

No MeSH data available.


Deletion of the Chrnb4 gene does not affect ethanol consumption. Data (mean ± SEM) represent average 24 h ethanol consumption (a), ethanol preference (b), and total fluid consumption (c). Female WT = 9, HET = 9, KO = 7
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Fig1: Deletion of the Chrnb4 gene does not affect ethanol consumption. Data (mean ± SEM) represent average 24 h ethanol consumption (a), ethanol preference (b), and total fluid consumption (c). Female WT = 9, HET = 9, KO = 7

Mentions: The Chrnb4 gene did not influence choice ethanol consumption (Fig. 1). Ethanol consumption, preference, and total fluid intake varied as a factor of ethanol concentration, but there were no significant main effects of strain or strain × concentration interactions observed. When we analyzed ethanol consumption, there was a significant main effect of concentration (F3,66 = 37.1, p < 0.05). Ethanol consumption increased as the concentration rose to 10%, but leveled off after this concentration (all p < 0.05; Fig. 1a). No interaction between concentration and strain for ethanol consumption was detected. A significant main effect of concentration (F3,66 = 74.7, p < 0.05) was detected for ethanol preference. There was no interaction between strain and concentration for ethanol preference. Ethanol preference showed an inverted U-shaped pattern (Fig. 1b). Preference increased from 3 to 7%, remaining constant between 7 and 10% and then decreased at 20% (all p < 0.001). When total fluid consumption was examined there was a significant main effect of concentration (F3,66 = 8.9, p < 0.05). Mice drank significantly more fluid at 20% compare to all other concentrations (all p < 0.05; Fig. 1c). No other significant effects were observed. All behavioral data split and graphed by sex can be seen in the manuscript’s additional files (see Additional file 2).Fig. 1


No evidence of a role of the β 4 subunit of the nicotinic acetylcholine receptor in alcohol-related behaviors
Deletion of the Chrnb4 gene does not affect ethanol consumption. Data (mean ± SEM) represent average 24 h ethanol consumption (a), ethanol preference (b), and total fluid consumption (c). Female WT = 9, HET = 9, KO = 7
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5382442&req=5

Fig1: Deletion of the Chrnb4 gene does not affect ethanol consumption. Data (mean ± SEM) represent average 24 h ethanol consumption (a), ethanol preference (b), and total fluid consumption (c). Female WT = 9, HET = 9, KO = 7
Mentions: The Chrnb4 gene did not influence choice ethanol consumption (Fig. 1). Ethanol consumption, preference, and total fluid intake varied as a factor of ethanol concentration, but there were no significant main effects of strain or strain × concentration interactions observed. When we analyzed ethanol consumption, there was a significant main effect of concentration (F3,66 = 37.1, p < 0.05). Ethanol consumption increased as the concentration rose to 10%, but leveled off after this concentration (all p < 0.05; Fig. 1a). No interaction between concentration and strain for ethanol consumption was detected. A significant main effect of concentration (F3,66 = 74.7, p < 0.05) was detected for ethanol preference. There was no interaction between strain and concentration for ethanol preference. Ethanol preference showed an inverted U-shaped pattern (Fig. 1b). Preference increased from 3 to 7%, remaining constant between 7 and 10% and then decreased at 20% (all p < 0.001). When total fluid consumption was examined there was a significant main effect of concentration (F3,66 = 8.9, p < 0.05). Mice drank significantly more fluid at 20% compare to all other concentrations (all p < 0.05; Fig. 1c). No other significant effects were observed. All behavioral data split and graphed by sex can be seen in the manuscript’s additional files (see Additional file 2).Fig. 1

View Article: PubMed Central - PubMed

ABSTRACT

Background: Nicotinic acetylcholine receptors have gained attention in the last several years as mediators of alcohol-related behaviors. The genes that code for the &alpha;5, &alpha;3, and &beta;4 subunits (Chrna5, Chrna3, and Chrnb4, respectively) map adjacent to each other on human chromosome 15/mouse chromosome 9. Genetic variants in this region have been associated with alcohol phenotypes and mice that overexpress these three subunits have reduced ethanol intake. In the present experiments, we examined the role of the Chrnb4 gene in three ethanol behaviors: consumption, ataxia, and sedation. Wildtype, heterozygous, and knockout mice were tested for ethanol consumption with a 2-bottle choice procedure and the drinking-in-the-dark paradigm. Ethanol-induced ataxia was measured with the balance beam and dowel test. Finally, the sedative effects of ethanol were measured with the loss of righting reflex paradigm.

Results: We observed no significant genotypic effects on any of the ethanol behaviors examined, suggesting that the &beta;4 subunit is not involved in mediating these responses.

Conclusions: While we found no evidence for the involvement of the &beta;4 subunit in ethanol responses, it is possible that this subunit modulates other behaviors not tested and further work should address this before completely ruling out its involvement.

Electronic supplementary material: The online version of this article (doi:10.1186/s13104-017-2470-7) contains supplementary material, which is available to authorized users.

No MeSH data available.