Methamphetamine-induced changes in myocardial gene transcription are sex-dependent.

BACKGROUND Prior work demonstrated that female rats (but not their male littermates) exposed to methamphetamine become hypersensitive to myocardial ischemic injury. Importantly, this sex-dependent effect persists following 30 days of subsequent abstinence from the drug, suggesting that it may be mediated by long term changes in gene expression that are not rapidly reversed following discontinuation of methamphetamine use. The goal of the present study was to determine whether methamphetamine induces sex-dependent changes in myocardial gene expression and whether these changes persist following subsequent abstinence from methamphetamine. RESULTS Methamphetamine induced changes in the myocardial transcriptome were significantly greater in female hearts than male hearts both in terms of the number of genes affected and the magnitude of the changes. The largest changes in female hearts involved genes that regulate the circadian clock (Dbp, Per3, Per2, BMal1, and Npas2) which are known to impact myocardial ischemic injury. These genes were unaffected by methamphetamine in male hearts. All changes in gene expression identified at day 11 returned to baseline by day 30. CONCLUSIONS These data demonstrate that female rats are more sensitive than males to methamphetamine-induced changes in the myocardial transcriptome and that methamphetamine does not induce changes in myocardial transcription that persist long term after exposure to the drug has been discontinued.