Taar1 gene variants have a causal role in methamphetamine intake and response and interact with Oprm1
Year: 2019
Type: article
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.
Source: eLife
DOI: 10.7554/elife.46472
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: G1292976068, G2337873157, G2608493153, Biological Bases of Drug-Seeking Behavior, G274637282, G394782630, G4549838990, Opioid Sensitive GABA inputs to the Ventral Midbrain, Genetic Factors Underlying Risk for Methamphetamine Intake and Associated Traits, G789916345, Methamphetamine Abuse Research Center, G9000313456, G9000351282, Training in the pharmacology of abused drugs
OpenAlex ID: W2953936710