About this Research Topic
Addiction is a relapsing brain disease where an individual pathologically pursues reward and/or relief by substance use and other behaviors. Data from linkage and association studies have revealed that vulnerability to substance abuse and addiction has a heritable component. Classic behavioral genetics studies have demonstrated that alleles influencing addiction-related phenotypes can be enriched by selection in model organisms, providing the basis for discovery of genes influencing the vulnerable phenotype. The causal variants that influence SUD have small individual effects, but collectively they may account for a significant amount of the phenotypic variation among vulnerable individuals.
There are strong heritable components to the range of phenotypes and endophenotypes associated with SUD. Human genome-wide analyses have identified variants associated with several of these phenotypes. Classic behavioral genetics studies indicate that alleles influencing addiction-related phenotypes and endophenotypes can be identified in model organisms, providing the basis for the discovery of genes influencing these human phenotypes.
These animal models provide an opportunity to identify targeted and measurable aspects of the genetics, epigenetics, physiology and brain function that influence behaviors associated with substance use disorders.
This Research Topic will focus on current research using animal models and how they are being exploited to define the genetic architecture of SUD. Animal models are helping to elucidate the relationships among variants and environmental components of substance use disorders, including several substances of abuse (e.g. cocaine, opioids, nicotine, methamphetamines), genetic background, gene x gene (GxG; epistasis), gene x environment (GxE), and gene x drug (GxD) interactions.
Rodents have long been utilized as a model for human drug addiction and substance abuse research. For instance, conserved synteny between the human and rat genomes and comprehensive knowledge bases, e.g., Rat Genome Database (RGD), highlight the versatility of this organism.
This Research Topic will welcome articles from researchers developing advanced behavioral models (e.g. rat/mouse/zebrafish) and genetic models to screen for vulnerability or resistance to the SUD. This compendium will focus on high-throughput (HT) genetic analyses on these models which link behavioral phenotypes, and integrative genomic studies. Research papers on innovative methods for the analysis of large genetic and epigenetic dataset are also welcome.
• Development of outbred animal models to mimic human SUD
• Use of the Hybrid Rat Diversity Panel to identify and map phenotypes related to SUD
• Discovery of allelic variants, genomic alterations, and functional changes associated with addictive behaviors
• Sex differences in SUD behaviors and phenotypes
• Environmental impact in SUD behaviors and phenotypes
• Single cell and tissue transcriptomic analyses
• Microbiome alterations in SUD
• Role of expression quantitative trait loci (eQTLs).
• Chromosome conformation studies to assign causality to a variant and its regulated gene.
• Methods for the analysis of large genetic and epigenetic datasets
Keywords: Substance use disorders, Animal models, Genetics, Epigenetics, Gene-environment, Systems analysis
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