Oxidative Stress in the Prefrontal Cortex as a Factor Responsible for Morphine Administration-Related Depression in Rats

Abstract

We examined the possible role of oxidative stress in the prefrontal cortex for the development of depression induced by course morphine administration. Thirty-two male albino rats were divided into four groups: control intact (CI), control saline-treated (CS), morphine (5 mg/kg) treated (M), and treated by combined injections of morphine in the above dose and 100 mg/kg N-acetylcysteine (M+NAC). Injections were performed daily during 14 days. After this, all animals were subjected to the forced swimming test. In all groups, after the experiment, the prefrontal cortex was removed and subjected to the assessment of oxidative stress. Rats of group M demonstrated a dramatic (severalfold) increase in the period of immobility in the swimming test, i.e., showed clear depressive behavior in this test. The malondialdehyde level in the prefrontal cortex of morphine-treated animals was much higher, while that of glutathione was significantly lower than those in animals of the control groups. The nitrite/nitrate ratio was also significantly lower in the M group. In group M+NAC, all above indices demonstrated clear trends to nearly full normalization. Thus, our experiments support the statement that morphineinduced depressive behavior develops, to a significant extent, due to intense oxidative stress in the prefrontal cortex. The above facts should, probably, be taken into account in the treatment of morphine addiction.