Introduction: Chronic
high doses of morphine inhibit cell proliferation and induce cell death. One of
the centers in reward pathway is the ventral tegmental area (VTA). Stimulation
of opioid receptors in the reward circuit in the brain by morphine could be
enabling a factor induce apoptosis in some brain regions, and expression of
death receptors increases on the cell surface. This study was designed to
evaluate the effect of morphine on changes in apoptotic factors (Bax/Bcl-2,
PARP and caspase-3) in the VTA during the acquisition of morphine-induced
conditioned place preference (CPP) and extinction period. Materials
and Methods: In
this study, in behavioral experiments, the CPP paradigm was done on 64 adult
male albino Wistar rats. In saline-control and three doses of morphine (0.5, 5,
10 mg/kg) experimental groups in acquisition, in addition with effective dose
of morphine (5 mg/kg) evaluate extinction period (8 days). Then, in the
molecular section the changes in apoptotic proteins assess with western blot
technique. Results: We
found that apoptotic factors increase in all three experimental groups in
response to morphine. However, the most response was significantly occurred at
the dose of 5 mg/kg morphine. Additionally, there is no change has been seen in
the apoptotic factors during the extinction period. Conclusion: It
seems that morphine in all doses cause apoptosis, but quite contrary, by
increasing the dose of morphine, the number of receptors involved in apoptosis
increases and morphine’s neuroprotective effects are appeared.
Razavi Y, Katebi N, Zeighamy Alamdary S, Oryan S, Khodagholi F, Haghparast A. Changes in apoptotic factors caspase-3, PARP and Bax/Bcl-2 ratio in the ventral tegmental area after the acquisition and extinction of morphine-induced conditioned place preference in the rat. Koomesh 1392; 14 (4) :404-413 URL: http://koomeshjournal.semums.ac.ir/article-1-1884-en.html