Constitutive Genetic Deletion of Hcn1 Increases Alcohol Preference during Adolescence.
Constitutive Genetic Deletion of Hcn1 Increases Alcohol Preference during Adolescence.
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DOI：
10.3390/brainsci10110763
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发表时间：
2020-10-22
期刊：
影响因子：
3.3
通讯作者：
Harrison NL
中科院分区：
文献类型：
--
作者：
Salling MC;Harrison NL
超极化激活的环核苷酸门控通道（HCN）是超极化激活的阳离子电流（Ih）的基础，在调节细胞类型和脑区域的神经元兴奋性方面具有不同的作用。最近，HCN通道已被牵连在药物滥用，包括酒精的临床前模型。在啮齿类动物的前额叶皮层，HCN的表达和Ih的大小在青春期发育调节，并可能容易受到酒精的影响。在小鼠中，青春期的酗酒导致Ih持续降低，这与成年期的饮酒量增加相一致，但HCN通道对饮酒的直接作用尚不清楚。在这里，我们表明，Hcn 1的基因缺失导致纯合无效（HCN 1 −/−）雄性小鼠在间歇性2瓶选择任务中的酒精偏好增加，与野生型同窝小鼠相比，不影响糖精或奎宁偏好。内侧前额叶皮质锥体神经元中HCN 1的靶向病毒缺失导致HCN 1表达的逐渐丧失和青春期Ih幅度的降低，然而，这并没有显著影响酒精消费或偏好。我们的结论是，虽然HCN 1调节酒精偏好，内侧前额叶皮层中HCN 1的基因缺失似乎不是这种效果的位点。
The hyperpolarization-activated cyclic nucleotide-gated channel (HCN), which underlies the hyperpolarization-activated cation current (Ih), 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 Ih 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 Ih 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 Hcn1 causes an increase in alcohol preference on intermittent 2-bottle choice task in homozygous null (HCN1−/−) 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 Hcn1 expression and a reduction in Ih 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 Hcn1 in the medial prefrontal cortex does not appear to be the locus for this effect.
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影响因子：
--
作者：
Cannady R;Rinker JA;Nimitvilai S;Woodward JJ;Mulholland PJ
通讯作者：
Mulholland PJ
影响因子：
4.7
作者：
Joffe ME;Winder DG;Conn PJ
通讯作者：
Conn PJ
侧眶额皮质的失活会增加乙醇依赖性但非依赖性小鼠的饮用。
影响因子：
4.7
作者：
den Hartog C;Zamudio-Bulcock P;Nimitvilai S;Gilstrap M;Eaton B;Fedarovich H;Motts A;Woodward JJ
通讯作者：
Woodward JJ
影响因子：
25.8
作者：
Greenwood, Tiffany A.;Lazzeroni, Laura C.;Braff, David L.
通讯作者：
Braff, David L.
影响因子：
5.3
作者：
Capuzzo, Giulia;Floresco, Stan B.
通讯作者：
Floresco, Stan B.