Over the last decade, there has been an increase in illegal drug use and uncontrolled opioid abuse in patients with chronic pain, which is associated with unintentional trauma and is a major risk factor for tolerance and withdrawal, leading to overdose and death [1-5]. The attention of scientists in various fields of medicine is focused on the study of changes in organs and systems under the influence of drugs, in particular, both in clinical and experimental
areas [6-9]. In clinical studies it is indicated that when exposed to opioids there are signs of immunosuppression, which cause an increased risk of infectious diseases and the development of inflammation [5, 10, 11]. Toxic effects of drugs are manifested in all organs and systems, which
may have an indirect or direct effect on the organs of the oral cavity [6, 12-15]. The question of the role of bacterial flora in the etiology and initiation of periodontal disease is certainly actively studied as the improvement of microbiological methods and the accumulation of research results [16-19]. Today,
one of the main hypotheses remains that dental plaque microorganisms are a determining factor in the development and progression of the inflammatory process in the periodontium, which provoke the inflammatory process and directly affect the microbial status of the oral cavity [20- 23].There is also evidence that the role of microorganisms in the development of periodontitis is unclear, although some bacterial pathogens alone or as part of microbial groups may be particularly important [24]. Therefore, in order to prevent the development of periodontal disease and the occurrence of infectious foci in the oral cavity caused by bacterial biopellicle, it is important to determine the etiology and pathogenesis of this pathology in experimental animal models in order to further extrapolate these data to the clinic [25]. However, the relationship between the species and quantitative composition of the microbiota of tooth surface in the gingival margin and the development and progression of inflammation in the gingival mucosa under action of the opioid are controversial and needs further study using modern methods of microbiological research in the experiment.

The aim isto investigate changes in the microbiota ofdental biofilm at the end of the eighth, tenth and twelfth weeks of experimental opioid exposure. 
Materials and methods: The study was performed on 36 white outbred adult male rats, which were injected with the opioid analgesic nalbuphine in increasing doses (0,212 – 0,3 mg / kg) during 8, 10 and 12 weeks. Qualitative and quantitative composition of microbiota of dental biofilm was studied using statistical analysis. 
Results: After eight weeks of opioid exposure, changes in microbiocenosis of dental biofilm of rats were caused by a significant increase in saprophytic and opportunistic microbiota and an appearance of pathogenic species of indicator microbiota with potential periodontopathogenic action. At the end of the tenth week, a significant increase in the quantitative indicators of certain species of opportunistic microbiota and increase in the quantitative composition of pathogenic bacteria were determined. After twelve week of opioid exposure, a significant increase in the quantitative indicators of pathogenic microbiota of dental biofilm was detected. 
Conclusions: Changes in the qualitative and quantitative composition of the microbiocenosis of the dental biofilm at the end of 8, 10 and 12 weeks of opioid exposure were established, they were manifested by a significant increase in the quantitative indicators of certain species of opportunistic microorganisms and a significant increase in pathogenic microbiota in the dynamics, which led to the progression of dysbiotic changes and purulent-inflammatory process in the oral cavity of rats