According to the UN there are up to 21 million opiate users in the world. Despite the efforts of the world community, opioid consumption does not tend to decrease. However, opioids are widely used as anesthesia in the modern practical medicine, especially in surgical and oncology clinics. The development of narcotics pharmacotherapy requires the issuing prevention and correction activities against resulting side effects and complications, especially on the part of the brain that is sensitive to drug effects due to the peculiarities of its structure and function. There are a number of unresolved questions on the problem of structural adjustment of the white substance of the brain with the long-term use of narcotic drugs. Our study reveals a portion of the ultrastructural features of the restructuring of the white substance of the brain as a result of the long-term opioid nalbuphine administration. The purpose of the study was to establish the peculiarities of the ultrastructure of the white substance of the brain of white rats in the dynamics of the long-term opioid influence. Material and methods. The studies were performed on 24 sexually mature white male-rats with the initial mass of 160-180 g, aged 3 months. Fifteen animals were taken from the total number of experimental animals and were divided into three groups accordingly to the three series of experiments: the changes in the ultrastructure of the white substance of the rat brain after opioid nalbuphine administration for 2 weeks were studied in the first series of experiments (5 animals); the changes in the ultrastructure of the white substance of the brain in response to the administration of the same opioid for 4 weeks were studied in the second series of experiments (5 animals); the state of the ultrastructural organization of the white substance of the rat brain after the influence of nalbuphine for 6 weeks in the experiment was studied in the third series of experiments (5 animals). The remaining 9 white rats served as a control group, and they were injected with 0.9 % solution of sodium chloride. Modeling of opioid dependence in rats was achieved using the methodology according to the patent of Ukraine № 76564 (R. M. Onysko and others, 2013). The electron microscopic study of the white substance of the brain of white rats in conditions of the long-term nalbuphine influence was performed on electronic microscope UEMV–100K at the accelerating voltage of 75 kV and magnifications x 4000 - x 8000. Results and discussion. After 2 weeks of the experiment, the nerve fibers of the white substance of the brain still did not have signs of damage and their structure is practically consistent with control. Thickening and disorganization of the myelin sheath were detected in some myelinated fibers, in axoplasm, single mitochondria were hypertrophied. After 4 weeks of nalbuphine administration, the swelling of the axis cylinders of nerve fibers was revealed; the number of organelles was reducing in axoplasm. The destruction of myelin, the deformation of the myelin sheaths of nerve fibers, and separation of myelin were observed. After 6 weeks course of the experiment, non-myelinated nerve fibers were fragmented. Myelinated nerve fibers in the transverse section became irregular, as evidenced by ovals with stitches and invaginations, or stellar contours of myelin membranes surrounding nerve fibers. Conclusions. The first changes of the ultrastructure of the white substance of the brain were observed after 2 weeks of opioid nalbuphine administration to experimental animals and they were growing during the following periods of the experiment. The main manifestations of neuropathy in a 6-week nalbuphine administration were the destructuring of the axial cylinders of nerve fibers and glial cells.
Full text: PDF (Ukr) 833K