Efeitos do tratamento com lítio na memória aversiva, comportamentos relacionados à ansiedade e depressão e na expressão de BDNF em ratos
Lithium (Li) is the first choice to treat bipolar disorder, a psychiatric illness characterized by mood oscillations between mania and depression. However, studies have demonstrated that this drug might influence mnemonic process due to its neuroprotector, antiapoptotic and neurogenic effects. The u...
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| Formato: | Dissertação |
| Idioma: | por |
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Universidade Federal do Rio Grande do Norte
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| Endereço do item: | https://repositorio.ufrn.br/jspui/handle/123456789/17373 |
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| Resumo: | Lithium (Li) is the first choice to treat bipolar disorder, a psychiatric illness
characterized by mood oscillations between mania and depression. However,
studies have demonstrated that this drug might influence mnemonic process
due to its neuroprotector, antiapoptotic and neurogenic effects. The use of Li in
the treatment of cognitive deficits caused by brain injury or neurodegenerative
disorders have been widely studied, and this drug shows to be effective in
preventing or even alleviating the memory impairment. The effects of Li on
anxiety and depression are controversial and the relationship of the effects of
lithium on memory, anxiety and depression remain unknown. In this context,
this study aims to: evaluate the effects of acute and chronic administration of
lithium carbonate in aversive memory and anxiety, simultaneously, using the
plus maze discriminative avoidance task (PMDAT); test the antidepressant
effect of the drug through the forced swimming test (FS) and analyze brainderived
neurotrophic factor (BDNF) expression in structures related to memory
and emotion. To evaluation of the acute effects, male Wistar rats were
submitted to i.p. administration of lithium carbonate (50, 100 or 200 mg/kg) one
hour before the training session (PMDAT) or lithium carbonate (50 or 100
mg/kg) one hour before the test session (FS). To evaluation of the chronic
effects, the doses administered were 50 or 100 mg/kg or vehicle once a day for
21 days before the beginning of behavioral tasks (PMDAT and FS). Afterwards,
the animals were euthanized and their brains removed and submitted to
immunohistochemistry procedure to quantify BDNF. The animals that received
acute treatment with 100 and 200 mg/kg of Li did not discriminated between the
enclosed arms (aversive and non-aversive) in the training session of PMDAT,
showing that these animal did not learned the task. This lack of discrimination
was also observed in the test session, showing that the animals did not recall
the aversive task. We also observed an increased exploration of the open arms
of these same groups, indicating an anxiolytic effect. The same groups showed
a reduction of locomotor activity, however, this effect does not seem to be
related with the anxiolytic effect of the drug. Chronic treatment with Li did not
promote alterations on learning or memory processes. Nevertheless, we
observed a reduction of open arms exploration by animals treated with 50
mg/kg when compared to the other groups, showing an anxiogenic effect
caused by this dose. This effect it is not related to locomotor alterations since
there were no alterations in these parameters. Both acute and chronic treatment
were ineffective in the FS. Chronic treatment with lithium was not able to modify
BDNF expression in hippocampus, amygdala and pre-frontal cortex. These
results suggest that acute administration of lithium promote impairments on
learning in an aversive task, blocking the occurrence of memory consolidation
and retrieval. The reduction of anxiety following acute treatment may have
prevented the learning of the aversive task, as it has been found that optimum
levels of anxiety are necessary for the occurrence of learning with emotional
context. With continued, treatment the animals recover the ability to learn and
recall the task. Indeed, they do not show differences in relation to control group,
and the lack of alterations on BDNF expression corroborates this result.
Possibly, the regimen of treatment used was not able to promote cognitive
improvement. Li showed acute anxiolytic effect, however chronic administration
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promoted the opposite effect. More studies are necessary to clarify the potential
beneficial effect of Li on aversive memory |
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