Sex influences susceptibility to methamphetamine cardiomyopathy in mice

In this study, we created a mouse model of methamphetamine cardiomyopa- thy that reproduces the chronic, progressive dosing commonly encountered in addicted subjects. We gradually increased the quantity of metham- phetamine given to C57Bl/6 mice from 5 to 40 mg/kg over 2 or 5 months during two study periods. At the fifth month, heart weight was increased, echocardiograms showed a dilated cardiomyopathy and survival was lower in males, with less effect in females. Interestingly, these findings correspond to previous observations in human patients, suggesting greater male suscepti- bility to the effects of methamphetamine on the heart. Transcriptional analy- sis showed changes in genes dysregulated in previous methamphetamine neurological studies as well as many that likely play a role in cardiac response to this toxic stress. We expect that a deeper understanding of the molecular biology of methamphetamine exposure in the heart will provide insights into the mechanism of cardiomyopathy in addicts and potential routes to more effective treatment.