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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 modulate consumption of saccharin or quinine. Data (mean ± SEM) represent average 24 h saccharin consumption (a), saccharin preference (b), total fluid consumption during saccharin availability (c), quinine consumption (d), quinine preference (e), total fluid consumption during quinine availability (f). Female WT = 9, HET = 9, KO = 7
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Fig2: Deletion of the Chrnb4 gene does not modulate consumption of saccharin or quinine. Data (mean ± SEM) represent average 24 h saccharin consumption (a), saccharin preference (b), total fluid consumption during saccharin availability (c), quinine consumption (d), quinine preference (e), total fluid consumption during quinine availability (f). Female WT = 9, HET = 9, KO = 7

Mentions: To determine if the Chrnb4 gene influenced taste sensitivity, we examined consumption of a sweet (saccharin) and bitter (quinine) noncaloric tastant (Fig. 2). Consumption, preference, and total fluid intake varied as a factor of saccharin or quinine concentration, but no significant main effects of strain or strain x concentration interactions were observed. A significant main effect of concentration (F1,22 = 531.5, p < 0.05) on saccharin consumption was observed. Saccharin consumption increased as the concentration rose to from 0.033 to 0.066% (Fig. 2a; mean ± SEM: 113.5 ± 3.2 vs. 279.3 ± 8.8, respectively). Preference for the saccharin-containing solution increased as the concentration of saccharin increased evidenced by a significant main effect of concentration (F1,22 = 5.6, p < 0.05, 0.033%: 0.94 ± 0.01 vs. 0.066%: 0.97 ± 0.01). There was no significant main effect of strain or interaction between strain × concentration for saccharin preference (Fig. 2b). There was a significant main effect of concentration on total fluid consumption (F1,22 = 87.0, p < 0.05). Mice drank significantly more fluid when 0.066% saccharin was available (0.033%: 8.5 ± 0.3, 0.066%: 10.3 ± 0.3) (Fig. 2c).Fig. 2


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 modulate consumption of saccharin or quinine. Data (mean ± SEM) represent average 24 h saccharin consumption (a), saccharin preference (b), total fluid consumption during saccharin availability (c), quinine consumption (d), quinine preference (e), total fluid consumption during quinine availability (f). Female WT = 9, HET = 9, KO = 7
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Fig2: Deletion of the Chrnb4 gene does not modulate consumption of saccharin or quinine. Data (mean ± SEM) represent average 24 h saccharin consumption (a), saccharin preference (b), total fluid consumption during saccharin availability (c), quinine consumption (d), quinine preference (e), total fluid consumption during quinine availability (f). Female WT = 9, HET = 9, KO = 7
Mentions: To determine if the Chrnb4 gene influenced taste sensitivity, we examined consumption of a sweet (saccharin) and bitter (quinine) noncaloric tastant (Fig. 2). Consumption, preference, and total fluid intake varied as a factor of saccharin or quinine concentration, but no significant main effects of strain or strain x concentration interactions were observed. A significant main effect of concentration (F1,22 = 531.5, p < 0.05) on saccharin consumption was observed. Saccharin consumption increased as the concentration rose to from 0.033 to 0.066% (Fig. 2a; mean ± SEM: 113.5 ± 3.2 vs. 279.3 ± 8.8, respectively). Preference for the saccharin-containing solution increased as the concentration of saccharin increased evidenced by a significant main effect of concentration (F1,22 = 5.6, p < 0.05, 0.033%: 0.94 ± 0.01 vs. 0.066%: 0.97 ± 0.01). There was no significant main effect of strain or interaction between strain × concentration for saccharin preference (Fig. 2b). There was a significant main effect of concentration on total fluid consumption (F1,22 = 87.0, p < 0.05). Mice drank significantly more fluid when 0.066% saccharin was available (0.033%: 8.5 ± 0.3, 0.066%: 10.3 ± 0.3) (Fig. 2c).Fig. 2

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.