The Expression Of BDNF, BCL-2 And Ultrastructural Changes During Morphine Dependence And Withdrawal In The Brains Of Mice

Objective: Previous researches have shown that opioid dependence led to morphological and structural changes of neurons in the relative brain areas. The present study was designed to assess the influence of chronic morphine administration and withdrawal on the ultrastructure and the expression of BDNF, Bcl-2 as well as their mRNA in brain regions, and to explicate the relationship between the expression of BDNF, Bcl-2 and the structural changes of neurons in the relative brain areas as a result of opioid dependence.Method: The expression of BDNF, Bcl-2 mRNA was investigated by in situ hybridization in the ventral tegmental areas, nucleus accumbens, locus coeruleus, prefrontal cortex and hippocampus. The levels of BDNF,Bcl-2 in these brain regions were measured by immunohistochemistry and the ultrastructural changes of the brain cells in the ventral tegmental areas and locus coeruleus of rats were examined by electron microscope.Result: Chronic morphine treatment and withdrawal significantly increased the levels of BDNF and their mRNA in the prefrontal cortex, locus coeruleus and the hippocampus, but marked decreased the levels of Bcl-2 protein and Bcl-2 mRNA compared with the control group in the ventral tegmental area, the locus coeruleus, the prefrontal cortex and the hippocampus of morphine dependence or withdrawal mice. Chronic morphine withdrawal resulted in an enhancement on the levels of Bcl-2 as well as Bcl-2 mRNA in the nucleus accumbens compared with the morphine dependence group. No alterations of BDNF and their mRNA in the ventral tegmental area and the nucleus accumbens were detected. There were ultrastructural changes in the ventral tegmental area and the locus coeruleus of morphine dependence mice.Conclusion: The levels of BDNF and Bcl-2 were altered in some brain regions after morphine dependence and withdrawal. There is a relationship between the development of opioid dependence and withdrawal and the changes of BDNF, Bcl-2 expression. However ,the changes in the levels of BDNF and Bcl-2 were not consistent in different brain regions ,indicating that involvement of BDNF and Bcl-2 in opioiddependence and withdrawal is complex and requires more rigorous examination. The ultrastructural changes in some of the brain regions confirmed that morphine dependence led to structural changes in the brain tissue.