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Taar1 gene variants have a causal role in methamphetamine intake and response and interact with Oprm1.


ABSTRACT: We identified a locus on mouse chromosome 10 that accounts for 60% of the genetic variance in methamphetamine intake in mice selectively bred for high versus low methamphetamine consumption. We nominated the trace amine-associated receptor 1 gene, Taar1, as the strongest candidate and identified regulation of the mu-opioid receptor 1 gene, Oprm1, as another contributor. This study exploited CRISPR-Cas9 to test the causal role of Taar1 in methamphetamine intake and a genetically-associated thermal response to methamphetamine. The methamphetamine-related traits were rescued, converting them to levels found in methamphetamine-avoiding animals. We used a family of recombinant inbred mouse strains for interval mapping and to examine independent and epistatic effects of Taar1 and Oprm1. Both methamphetamine intake and the thermal response mapped to Taar1 and the independent effect of Taar1 was dependent on genotype at Oprm1. Our findings encourage investigation of the contribution of Taar1 and Oprm1 variants to human methamphetamine addiction.

SUBMITTER: Stafford AM 

PROVIDER: S-EPMC6682400 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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<i>Taar1</i> gene variants have a causal role in methamphetamine intake and response and interact with <i>Oprm1</i>.

Stafford Alexandra M AM   Reed Cheryl C   Baba Harue H   Walter Nicole Ar NA   Mootz John Rk JR   Williams Robert W RW   Neve Kim A KA   Fedorov Lev M LM   Janowsky Aaron J AJ   Phillips Tamara J TJ  

eLife 20190709


We identified a locus on mouse chromosome 10 that accounts for 60% of the genetic variance in methamphetamine intake in mice selectively bred for high versus low methamphetamine consumption. We nominated the trace amine-associated receptor 1 gene, <i>Taar1</i>, as the strongest candidate and identified regulation of the mu-opioid receptor 1 gene, <i>Oprm1</i>, as another contributor. This study exploited CRISPR-Cas9 to test the causal role of <i>Taar1</i> in methamphetamine intake and a genetica  ...[more]

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