Continued methamphetamine (MA) use is influenced by sensitivity to its aversive effects. This dissertation examined genetic and physiological factors underlying the inverse relationship between MA consumption and MA‑induced conditioned taste aversion (CTA) using selectively bred mouse lines with high or low MA intake. Results demonstrate that methamphetamine consumption and aversion are strongly associated with genotype at the Taar1 gene, which encodes the trace amine‑associated receptor 1. Functional TAAR1 increased sensitivity to aversive physiological responses, including hypothermia and elevated corticosterone, and reduced MA intake. Additional findings suggest serotonin transporter activity contributes to aversive sensitivity. These results indicate that TAAR1‑mediated aversive effects play a key role in limiting voluntary MA consumption and may protect against MA use.
