Document Type : Original Article
Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran
Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Biological Research Center, Imam Hossein Comprehensive University, Tehran, Iran
Objective: In this study we have investigated the changes in D2 receptor expression level in morphine-sensitized mice, in the absence and presence of lithium chloride (LiCl). The result would pave the way to comprehend and confront this complicated event.
Materials and Methods: Male NMRI mice, weighing 20-25g, were used in this study. They were divided into six groups. The first group received 0.9% saline as the control group and the other group was treated with morphine sulphate (30 mg/kg). LiCl (5 and 10 mg/kg treatments) was separately performed in two other groups. The final two groups were simultaneously treated with morphine sulphate (30 mg/kg) and LiCl (5 mg/kg) in one group and morphine sulphate (30 mg/kg) accompanied by LiCl (10 mg/kg) in the other group. All injections were performed intraperitoneally and once daily. After a five day wash-out, mice were decapitated and the brain regions which included the striatum, prefrontal cortex (PFC) and hippocampus were extracted. Using relative Real-Time polymerase chain reaction (PCR), the expression levels of the long (D2L) and short (D2S) isoforms of the D2 receptor were investigated.
Results: Morphine treatment leads to a significant increase (p<0.0.5) in D2S levels in the striatum and PFC but has no effect on D2L levels in the examined regions. In the group receiving LiCl 5mg/kg, the D2L levels showed a significant augmentation in PFC and the hippocampus (p<0.05) as well as the striatum (p<0.001). The D2S levels in the same group, significantly increased in the PFC (p<0.05) and striatum (p<0.001). LiCl at a dose of 10 mg/kg did not alter the expression of either isoforms in any region. While simultaneous administration of morphine and LiCl (10 mg/kg) resulted in a marked increase in D2S levels in the striatum (p<0.001) and PFC (p<0.05), morphine administration along with LiCl (5mg/kg) was ineffective on the expression levels of D2L and D2S isoforms when compared to the control group.
Conclusion: Morphine sensitization leads to an increase in D2S receptor expression and is affected by lithium in a dose-dependent manner where the lower dose inhibits and higher dose to enhances this effect. It is assumed that sensitization-induced changes in the transcript level are more regulated by dopamine transmission rather than by the direct effect of morphine and/or lithium on gene expression.