Effect Of Morphine-Sensitization In D2 Receptor Gene Expression In The Mice Brain In The Absence And Presence Of Lithium Chloride

Document Type : Original Article


1 Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

2 Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran

4 Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran

5 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.