Methamphetamine Induces Sex-Dependent Changes in Gene Expression in Male and Female Hearts

Male and female rats received daily injections of saline or methamphetamine for 10 days. Changes in gene expression were assessed by RNA sequencing either 24 hours or 30 days following the last injection. 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 is known to impact myocardial sensitivity to ischemia. These genes were unaffected by methamphetamine in male hearts. All changes in gene expression identified at day 11 returned to baseline by day 30. 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. Overall design: Gene expression profiling of cardiac tissue of male and female rats following treatment with methamphetamine or saline, with and without 30 days of abstinence following treatment.