Efeitos comportamentais do metilfenidato e da reboxetina em modelo animal de déficit de atenção induzido pela lesão por etanol em camundongos

• Ano de defesa: 2008
• Autor(a) principal: Ribeiro, Monique Vieira
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Palavras-chave em Português: Etanol; Metilfenidato; Camundongos
• Link de acesso: http://www.repositorio.ufc.br/handle/riufc/2589

Attention Deficit and Hyperactivity Disorder (ADHD) is a neurobehavioral disorder that affects between 3 - 5% of scholar-aged children. The disorder is characterized by inattention, hyperactivity and impulsivity. Children exposed to alcohol during pregnancy may exhibit hyperactivity, language and learning deficits. Dopamine and Norepinephrine seem to have an important role in the pathophysiology, which is confirmed by the response to psychostimulants, which increase the availability of these neurotransmitters in the synaptic cleft. The psychostimulant Methylphenidate is the gold-standard in the treatment of ADHD. Non-stimulant medications, such as norepinephrine reuptake inhibitor Reboxetine are gaining space as an alternative in the treatment of ADHD. In rats, when ethanol is given during the period of brain development, it may cause pre-frontal circuits’ dysfunction and abnormal dopaminergic transmission. The aim of this work is to evaluate the behavioral effects (attention, memory, motor activity, anxiety and depression) of Methylphenidate (MPH) and Reboxetine (RBX) in an experimental model of attention deficit induced by ethanol in mice. Male and female Swiss mice on the post-natal day 10 were injected with ethanol (2 x 2,5g/kg, s.c., 6 h-interval) or saline (same volume). On post-natal day 30, behavioral testing was started (T-maze, Y-maze, passive avoidance, forced swim test, open field, plus maze and dark/light box). The subjects received either MPH (2,5mg/kg) or RBX (10 mg/kg) p.o, 30 minutes before each test session. There were no histopathologic changes in cerebral cortex of mice that received ethanol. In the T-maze, ethanol subjects had significant attention deficits, taking a longer time to learn, but these were reversed by MPH and RBX (Cont. 1,5±0,32, Et 7,18±0,32, MPH+Et 3,14±0,88, RBX+Et 1,55±0,33). During delayed discrimination, ethanol group had memory deficits, with fewer correct choices than controls. MPH ameliorated the deficits, but RBX did not (Cont. 25,78±0,86, Et 21,27±1,02, MPH+Et 25,14±1,03, RBX+Et 21,88±1,00). There were no deficits in aversive memory during passive avoidance test. In the Y-Maze, ethanol subjects had working memory deficits, that were mitigated MPH, but not by RBX. (Cont. 73,28±4,75, Et 43,53±4,65, MPH+Et 60,57±1,92, RBX+Et 54,63±2,80) . At the open field, ethanol subjects had motor hypoactivity that was reversed by MPH and RBX (Cont. 93,59±6,38, Et 66,52±5,87, MPH+Et 98,14±9,23, RBX+Et 77,3±7,68). At the Light/dark paradigm, ethanol subjects displayed anxious behavior, remaining more time in the dark side and this behavior was reversed by RBX only (Cont. 149±5,99, Et 115,4±4,27, MPH+Et 120,1±6,81, RBX+Et 149,1±2,55). At the Plus-Maze, ethanol subjects had an anxiogenic behavior, remaining less time in the open arms, and this effect was reversed by RBX (Cont. 88,06±12,52, Et 50,53±5,99, MPH+Et 39,86±12,00, RBX+Et 86,29±9,49). At the forced swimming test, ethanol subjects had prolonged immobility, which was not reversed by MPH or RBX (Cont. 74,17±23,43, Et 141,8±19,3, MPH+Et 178,9±12,43, RBX+Et 118,5±18,25). In conclusion, mice exposed to ethanol during brain development have attention and memory deficits that are reversed by MPH and partially by RBX. RBX may be used as a second line treatment in subjects that do not respond to stimulants or have comorbid anxiety.