The Effect of Aerobic Training and Berberine Supplementation on the Expression of Dopamine 4 Receptor and CREB Gene in Heart Tissue of Female Rats During Withdrawal from Methamphetamine

Methamphetamine increases the release of dopamine from nerve terminals. Binding of dopamine to dopamine receptors increases the phosphorylation of cyclic adenosine monophosphate responsive element (CREB) protein and changes the transcription of downstream genes.The purpose of this study is to investigate the effect of methamphetamine induction followed by aerobic training and Berberine on dopamine receptor 4 and CREB gene expression in the heart tissue of methamphetamine-addicted female rats during the withdrawal period.

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

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).

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.