Effect of Morphine-Sensitization in D ReceptorGene Expression in the Mice Brain in the Absenceand Presence of Lithium Chloride

In this study we have investigated the changes in D 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.

Male NMRI mice, weighing 0-5g, 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 (0 mg/kg). LiCl (5 and 0 mg/kg treatments) was separately performed in two other groups. The final two groups were simultaneously treated with morphine sulphate (0 mg/kg) and LiCl (5 mg/kg) in one group and morphine sulphate (0 mg/kg) accompanied by LiCl (0 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 (DL) and short (DS) isoforms of the D receptor were investigated.

Morphine treatment leads to a significant increase (p<0.0.5) in DS levels in the striatum and PFC but has no effect on DL levels in the examined regions. In the group receiving LiCl 5mg/kg, the DL levels showed a significant augmentation in PFC and the hippocampus (p<0.05) as well as the striatum (p<0.00). The DS levels in the same group, significantly increased in the PFC (p<0.05) and striatum (p<0.00). LiCl at a dose of 0 mg/kg did not alter the expression of either isoforms in any region. While simultaneous administration of morphine and LiCl (0 mg/kg) resulted in a marked increase in DS levels in the striatum (p<0.00) and PFC (p<0.05), morphine administration along with LiCl (5mg/kg) was ineffective on the expression levels of DL and DS isoforms when compared to the control group.

Morphine sensitization leads to an increase in DS 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.