Hnrnph1 is a novel regulator of alcohol reward.
Hnrnph1 is a novel regulator of alcohol reward.
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DOI：
10.1016/j.drugalcdep.2021.108518
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发表时间：
2021-03-01
影响因子：
4.2
通讯作者：
Szumlinski KK
中科院分区：
文献类型：
--
作者：
Fultz EK;Coelho MA;Lieberman D;Jimenez-Chavez CL;Bryant CD;Szumlinski KK
Hnrnph1是甲基苯丙胺行为敏感性的有效数量性状基因，编码异质性核糖核蛋白H1(HnRNP H1)。这种RNA结合蛋白参与RNA代谢的所有阶段，影响中皮质边缘多巴胺的神经传递，从而影响与成瘾相关的行为。我们研究了Hnrnph1(Hnrnph1+/−)第一个编码外显子缺失杂合子小鼠的酒精行为表型。我们检查了酒精摄入量在连续和有限接触程序下的情况，以及酒精诱导的场所条件反射。随访研究考察了急性酒精和重复酒精对精神运动激活和镇静催眠作用的基因差异，并采用行为测试组合来确定Hnrnph1缺失对酒精戒断过程中负性情绪表现的影响。与野生型(WT)对照组相比，Hnrnph1+/−男性在两种饮酒程序下都表现出钝性的高酒精摄入量。Hnrnph1缺失不影响低剂量酒精的条件性奖赏特性，但逆转了高剂量酒精(2和4g/kg)引发的条件性位置厌恶，对雄性小鼠的影响比对雌性小鼠更强烈。未观察到酒精诱导的运动活动的基因差异。Hnrnph1+/−小鼠对酒精镇静催眠作用的敏感性略有增加，但在对酒精镇静催眠作用或酒精代谢的耐受性方面与WT小鼠无差异，在戒断诱导的负性情绪模型中观察到Hnrnph1缺失的影响不一致。这些数据确定Hnrnph1是一种新的、男性选择性的酒精消费和高剂量酒精厌恶的驱动因素，这可能与酒精滥用和酒精中毒的神经生物学有关。
Hnrnph1 is a validated quantitative trait gene for methamphetamine behavioral sensitivity that encodes for heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1). This RNA-binding protein is involved in all stages of RNA metabolism that impacts mesocorticolimbic dopamine neurotransmission to influence addiction-related behavior. We characterized the alcohol behavioral phenotypes of mice heterozygous for a deletion in the first coding exon of Hnrnph1 (Hnrnph1+/−). We examined alcohol intake under both continuous- and limited-access procedures, as well as alcohol-induced place-conditioning. Follow-up studies examined genotypic differences in the psychomotor-activating and sedative-hypnotic effects of acute and repeated alcohol, and a behavioral test battery was employed to determine the effects of Hnrnph1 deletion on the manifestation of negative affect during alcohol withdrawal. Relative to wild-type (WT) controls, Hnrnph1+/− males exhibited blunted intake of high alcohol concentrations under both drinking procedures. Hnrnph1 deletion did not impact the conditioned rewarding properties of low-dose alcohol, but reversed the conditioned place-aversion elicited by higher alcohol doses (2 and 4 g/kg), with more robust effects in male versus female mice. No genotypic differences were observed for alcohol-induced locomotor activity. Hnrnph1+/− mice exhibited a modest increase in sensitivity to alcohol’s sedative-hypnotic effects, but did not differ from WT mice with regard to tolerance to alcohol’s sedative-hypnotic effects or alcohol metabolism, Inconsistent effects of Hnrnph1 deletion were observed in models for withdrawal-induced negative affect. These data identify Hnrnph1 as a novel, male-selective, driver of alcohol consumption and high-dose alcohol aversion that is potentially relevant to the neurobiology of alcohol abuse and alcoholism.
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DOI：
10.1016/j.pnpbp.2015.07.011
发表时间：
2016-02-04
影响因子：
5.6
作者：
Berrettini, Wade
通讯作者：
Berrettini, Wade
影响因子：
1.9
作者：
Cunningham, Christopher L.
通讯作者：
Cunningham, Christopher L.
DOI：
10.1177/2470547017712985
发表时间：
2017-01
期刊：
Chronic stress (Thousand Oaks, Calif.)
影响因子：
--
作者：
Lee KM;Coelho MA;Sern KR;Class MA;Bocz MD;Szumlinski KK
通讯作者：
Szumlinski KK
影响因子：
3.4
作者：
CUNNINGHAM, CL;NIEHUS, DR;PRATHER, LK
通讯作者：
PRATHER, LK
DOI：
10.1111/gbb.12273
发表时间：
2016-01
期刊：
Genes, brain, and behavior
影响因子：
--
作者：
Bryant CD;Yazdani N
通讯作者：
Yazdani N