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Generalized anxiety disorder is one of the most common psychiatric disorders, affecting a high percentage of human beings around the world. This emotional disorder possesses marked gender differences and occurs more often in women than in men, in a proportion of . Accompanying the reproductive cycle of women are significant fluctuations in plasma and brain steroid hormone concentrations, including oestradiol, progesterone, and allopregnanolone, among others. These hormonal changes are related to some illnesses and with the development of anxiety and mood swings occurring in the premenstrual and postpartum period, and particularly during the menopause. Menopause is a clinical term used to indicate the cessation of the woman's reproductive ability that occurs naturally, but also may be surgically induced by bilateral oophorectomy, with or without the removal of the Fallopian tubes and uterus. Natural menopause includes specific periods related to the physiological and hormonal changes produced by ovarian failure, it is usually a natural stage that occurs to women in midlife, during their late s or early s, indicating the end of the reproductive period in the woman. During the menopause transition years, women experience changes in the production of ovarian hormones, which are associated with significant changes in the physiological, emotional, and affective processes. Unfortunately, surgical menopause occurs at an early age, and produces similar physiological and psychiatric disorders, but they are more severe in this instance. In both cases, typical symptoms associated with menopause critically deteriorate the mental health of the women. In this way, the therapeutic management of clinical symptoms of menopause include replacement hormone therapy, the use of anxiolytic and antidepressant drugs, and other natural alternatives based on the use of chemical compounds obtained from plants such as soya. However, a general effective treatment for menopause symptoms does not yet exist. For this reason, experimental studies have proposed ovariectomy in rats as a potential tool to study the effects of a long-term absence of ovarian hormones associated with surgical menopause, which also allowed the study of substances with potential therapeutic application to ameliorate typical symptoms associated with surgical menopause. The aim of this chapter is to review the participation of ovarian hormones in the regulation of emotional and affective disorders in women with natural or surgical menopause particularly their anatomical pathways, neurotransmission systems, and the resulting behavioural patterns. Finally, preclinical and clinical research suggested that longterm absence of ovarian hormones associated with natural or surgical menopause is the principal cause of physiological and psychiatric disorder in the women therefore, oestrogenic compounds seem to play an important role in the maintenance of the brain structures that regulate anxiety, mood, memory, and cognitive functions in menopausal women.

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The 5-HTergic system and particularly 5-HT(2A) receptors have been involved in prefrontal cognitive functions, but the underlying mechanisms by which the serotonin (5-HT) system modulates these processes are still unclear. In this work, the effects of prefrontal 5-HTergic denervation on the density and expression levels of 5-HT(2A) receptors were evaluated by immunohistochemical and molecular biology studies in the prefrontal cortex (PFC). The [(3)H]-Ketanserin binding study revealed an increase in the B(max), along with no change in the binding affinity (K(D)) for 5-HT(2A) receptors. The increase in PFC of 5-HT(2A) receptor density in response to denervation was accompanied by increase in 5-HT(2A) receptor mRNA and protein levels. This increase in the number of 5-HT(2A) receptors may be interpreted as an adaptive plastic change, i.e., hypersensitivity; resulting from the selective pharmacological lesion of the raphe-proceeding 5-HTergic fibers to the PFC. Based on previous evidence, this could be strongly related to the abnormal expression of short-term memory.

Zebrafish (Danio rerio) is a popular and valuable species used in many different biomedical research areas. The complex behavior that fish exhibit in response to different stimuli allows researchers to explore the biological and pharmacological basis of affective and mood disorders. In this sense, anxiety is commonly studied in preclinical research with animal models in rodents. During the last decade, those models have been successfully adapted to zebrafish. Stressful stimuli, such as novel environments, chemical substances, light conditions, and predator images, can trigger defensive behaviors considered indicators of an anxiety-like state. In the first stage, models were adapted and validated with different stressors and anxiolytic drugs with promising results and are now successfully used to generate scientific knowledge. In that sense, zebrafish allows several routes of administration and other methodological advantages to explore the anxiolytic effects of natural products in behavioral tests as novel tank, light-dark chamber, and black/white maze, among others. The present work will review the main findings on preclinical research using adult zebrafish to explore anxiolytics effects of natural products as plant secondary metabolites such as flavonoids, alkaloids and terpenes or standardized extracts of plants, among others. Scientific literature confirms the utility of zebrafish tests to explore anxiety-like states and anxiolytic-like effects of plant secondary metabolites, which represent a useful and ethical tool in the first stages of behavioral.

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The prolonged ingestion of F may cause significant damage to health and particularly to the nervous system. Therefore, it is important to be aware of this serious problem and avoid the use of toothpaste and items that contain F, particularly in children as they are more susceptible to the toxic effects of F.