Materials and Methods: 30 rats were randomly divided into 5 control groups, methamphetamine, methamphetamine + aerobic training, methamphetamine + Berberine, methamphetamine + aerobic training + Berberine. Intraperitoneal injection of 10 mg/kg of methamphetamine was performed for 5 days, and during the withdrawal period, aerobic training was performed for 4 weeks and simultaneously the consumption of berberine 100 mg/kg as a solution in drinking water was considered. Real Time PCR method was used to measure gene expression. Independent T-test, Kruskal-Wallis test and SPSS24 software were used at the level of 0.05 to analyze the data.

  Ethical Considerations: The code of ethics in the research was received with number IR.IAU.SHAHROOD.REC.1402.015.

  findings: The results showed that methamphetamine use caused a non-significant increase (97%) in CREB expression and a non-significant decrease (52%) in dopamine 4 receptor compared to the control group (p>0.05). The implementation of interventions during the withdrawal period, such as Berberine consumption and the combination of berberine with aerobic training, produced non-significant increasing and decreasing effects on dopamine 4 receptor gene expression and CREB in the heart of methamphetamine-addicted rats, respectively (p>0.05).

  Conclusion: Short-term induction of methamphetamine did not cause significant changes in the expression of dopamine 4 receptor and CREB genes in the heart. Therefore, these genes could not undergo a significant change as a result of interventions such as Berberine and exercise. More studies are needed to investigate exact genetic changes in heart tissue.