Effect of Morphine-Sensitization in D2 Receptor Gene Expression in the Mice Brain in the Absence and Presence of Lithium Chloride

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.