The CDC reports that 52.9% of people who used MA in the last year have a MA use disorder. Quantitative trait locus mapping in selectively bred high and low MA drinking (MADR) mouse lines identified a single nucleotide polymorphism (SNP) that accounts for 60% of the genetically determined differences in MA intake in the MADR lines. This nonsynonymous substitution mutation within the trace amine-associated receptor 1 (Taar1) gene alters the protein amino acid sequence and results in the expression of a nonfunctional TAAR1 receptor. MA is a full TAAR1 agonist, and homozygosity for this mutation (Taar1m1J) segregates with high MA drinking and low sensitivity with MA-induced aversion. These results suggest that increased activation of NMDA receptors is important for aversive effects of MA. Sensitivity to MA-induced aversion via TAAR1 signaling may play an important protective role against developing MA use disorders.