Oral cancer is the most common malignancy in the head and neck region. Studies have demonstrated a relationship between oral cancer and psychoneuroendocrine mechanisms, such as the limbic-hypothalamic-pituitary-adrenal axis, which is closely involved with stress. Cancer patients display high levels of stress and anxiety, as well as having cognitive impairments, such as reduced memory and learning. To date, there have been no studies evaluating the impact of oral cancer on the morphology of hypothalamic paraventricular nucleus (NPH) and hippocampus (HC), two brain structures that may be involved in the pathogenesis of behavioral changes and psychic disorders. In the present study we will use a 4-nitroquinoline-1-oxide (4NQO) chemically induced oral cancer model to evaluate the effects of oral cancer on the anxiety-like behavior and morphology of NPH and HC. We will use three experimental groups: Group 1 (control), composed of 8 male Wistar rats who will not undergo treatment with the carcinogen; Group 2 (leukoplakia), composed of 8 male Wistar rats treated with the carcinogen 4NQO and presenting premalignant lesions and Group 3 (ECC), composed of 8 male Wistar rats treated with the carcinogen 4NQO and having Oral Squamous Cell Carcinoma (OSCC). When they reach adulthood (90 days) the animals from the experimental groups 2 and 3 will be treated with the carcinogen 4NQO for 120 days, when they will be submitted to euthanasia along with the control rats. Before the initiation and after 120 days of oral carcinogenesis induction by 4NQO the animals will undergo specific tests to evaluate the levels of anxiety. Von Frey method will be used to evaluate the occurrence and intensity of related-lesions orofacial pain. Clinical and histopathological analyzes will be performed to evaluate the occurrence of leukoplakia or OSCC. Tumor volumes will also be measured. Stereological technique will be used to obtain the total volume of NPH and HC, besides quantity and volume of NPH neurons. Statistical tests will assess the influence of 4NQO treatment on the anxiety behavior and brain morphological changes. We believe that this study will allow us to understand new parameters of Central Nervous System (CNS) changes associated with cancer.
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