Hnrnph1 is a novel regulator of alcohol reward

Elissa K Fultz; Michal A Coelho; Dylan Lieberman; C Leonardo Jimenez-Chavez; Camron D Bryant; Karen K Szumlinski

doi:10.1016/j.drugalcdep.2021.108518

Hnrnph1 is a novel regulator of alcohol reward

Drug Alcohol Depend. 2021 Mar 1:220:108518. doi: 10.1016/j.drugalcdep.2021.108518. Epub 2021 Jan 10.

Authors

Elissa K Fultz¹, Michal A Coelho¹, Dylan Lieberman¹, C Leonardo Jimenez-Chavez¹, Camron D Bryant², Karen K Szumlinski³

Affiliations

¹ Department of Psychological Brain Sciences, University of California, Santa Barbara, United States.
² Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry, Boston University School of Medicine, United States.
³ Department of Psychological Brain Sciences, University of California, Santa Barbara, United States; Department of Molecular, Developmental and Cellular Biology and the Neuroscience Research Institute, University of California, Santa Barbara, United States. Electronic address: szumlinski@ucsb.edu.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Binge-drinking; Dysphoria; Ethanol; Intoxication; Negative affect; Place-preference; hnRNP H1.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Affect / drug effects
Alcohol Drinking / genetics*
Alcoholic Intoxication
Animals
Behavior, Animal / drug effects
Exons*
Female
Gene Deletion*
Genotype*
Heterogeneous-Nuclear Ribonucleoproteins / genetics*
Locomotion / drug effects
Male
Mice
Models, Animal
Phenotype
Reward

Substances

Heterogeneous-Nuclear Ribonucleoproteins
Hnrnph1 protein, mouse

Abstract

Publication types

MeSH terms

Substances

Grants and funding