Prevenção pelo acido láurico de alterações mania símile em modelo experimental induzido por D-anfetamina

• Autor(a) principal: Barreto, Antônio Cláudio Barros
• Data de Publicação: 2020
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
• Texto Completo: http://www.repositorio.ufc.br/handle/riufc/55527
• topic: Transtorno Bipolar; Dextroanfetamina; Lítio; Anfetamina; Óleo de Coco

Bipolar disorder (TB) is a severe, chronic and prevalent psychiatric disorder affecting 1-2% of the world’s population. The disorder manifests as manic (agitation, hyperactivity, impulsivity) and / or depressive (depressed mood, fatigue, loss of energy, tendency to isolation) symptoms with a high risk of suicide. Mood stabilizers are the drugs used for their treatment although they have important side effects. It is worth mentioning that mood crisis prevention strategies are of great importance for the treatment of TB avoiding neuroprogression. In this context, lauric acid (LA), the most abundant fatty acid in coconut oil being the main component of the ketogenic diet (low in sugars and high in good fats) is a promising strategy. It is noteworthy that in recent years the ketogenic diet has shown positive results in combating mood symptoms, although by mechanisms still little known. In this context, in this study we evaluated the prevention of mania-like symptoms as well as neurobiological changes in rats submitted to the repeated d-amphetamine (AMPH) induced mania model. Therefore, lauric acid (LA) was used in two doses, 10 mg / kg and 20 mg / kg, orally, in adult male Wistar rats. These animals received saline solution (control group); amphetamine (2 mg / kg, i.p. - mania group); LA (10 or 20 mg / kg) or Lithium (Li - 47.5 mg / kg, i.p. - standard mood stabilizer), or with the LA + Li combination for 14 consecutive days. Behavioral assessment was done through open field test (locomotor activity), Y-maze (working memory assessment) and cat odor (risk behavior). Oxidative changes were also evaluated by determining levels of reduced glutathione (GSH), lipid peroxidation and nitrite, as well as neurotrophin Brain Derived Neurotrophic Factor (BDNF) in the prefrontal cortex (CPF), striated body (EC) and hippocampus. Behavioral test results showed that AMPH promoted increased locomotor activity, impaired working memory, and increased risk exposure, consistent with the TB mania phenotype. LA prevented locomotor and working memory changes, especially in the combined treatment LA20 + Li. Risk behavior was attenuated at all doses studied. In the neurochemical alterations evaluated, LA prevented the reduction of GSH levels mainly in CPF when combined with Li, as well as the increase of lipid peroxidation and increase of AMPH-induced nitrite levels (LA alone). There was an increase in BDNF levels in HC at the lowest dose of LA and Li. Taken together, the results suggest the possibility of LA being used as a preventive therapy for TB based on its antioxidant and neurotrophic mechanisms.