Modulação glutamatérgica pela memantina na memória operacional espacial em ratos sob estimulação epidural cortical por corrente contínua de baixa intensidade
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Data
2013-05-03
Autores
Alves, Natércia Carvalhal
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Universidade Federal do Espírito Santo
Resumo
Electrical brain stimulation paradigms are lately becoming a potential tool in cognitive neuromodulation of learning and memory. The translational research in animal models for elucidating the mechanisms underlying neuroplasticity is necessary. The neuronal activity in the prefrontal cortex (PFC) has been considered as the cellular correlate of working memory, defined as the cognitive process of retention and manipulation of information in the service of understanding, reasoning and planning. Delayed tasks in the eight-arm radial maze (RAM) are well established paradigms for spatial working memory studies. Memantine, an antagonist with moderate affinity of N-Methyl-D-Aspartate (NMDA) receptors (NMDAR), was used in the present study to investigate the glutamatergic modulation of spatial working memory in rats under epidural direct current stimulation (eDCS) over the left medial PFC (mPFC). Male Wistar rats previously trained in the RAM (n = 50) underwent surgery for epidural electrode implant (5.0 mm diameter) over the left mPFC. The animals’ performance was evaluated in 4- h and 10-h delayed tasks in the RAM, with (eDCS) and without (Sham) active epidural electric stimulation (400 μA, 10 min, cathode 50 mm diameter, 5 min before the task) combined with acute ip administrations of saline or memantine at doses of 0.32, 1.0 or 3.2 mg/kg, semi-randomly administered 30 min before the tasks. The eDCS group significantly committed fewer errors in the 10-h delay performance (1.46 ± 0.27), under saline, compared to Sham group (2.53 ± 0.40) (p < 0.05, Mann-Whitney test). Similarly, in the 4-h delayed task, eDCS decreased significantly the number of errors in animals with poor performance at baseline (> 2 errors under saline), eDCS (2.53 ± 0.31) and Sham (3.71 ± 0.47) (p < 0.05, Mann-Whitney test). Memantine at the dose of 1.0 mg/kg (1.91 ± 0.41) significantly impaired the 4-h post-delay performance of Sham animals with good baseline performance under saline treatment (0.36 ± 0.15) (p < 0.05, Friedman test followed by Dunn’s post-hoc), whereas memantine tended to improve the performance of animals with poor baseline performance but at non-statistically significant manner. In the eDCS subgroup of good baseline performance, memantine showed a propensity to increase the number of errors in 4-h post-delay performance, but the eDCS in animals with poor baseline performance combined with memantine, notably at the dose of 3.2 mg/kg (0.96 ± 0.31), significantly improved the 4-h post-delay performance when compared to saline (2.57 ± 0.30) (p < 0.05, Friedman test followed by Dunn’s post-hoc). Thus, the eDCS over the mPFC facilitated the long-term component of spatial working memory performance alone and also facilitated the improving effects of memantine in animals with poor baseline performance. The data suggest that eDCS involves NMDAR in its facilitatory effects on spatial working memory in a certain extent and depending on the baseline performance. Because of the mild interaction observed, NMDAR mediation does not seem to be a single glutamatergic mechanism. Thus, the involvement of other glutamatergic receptors in the eDCS effects on working memory has to be addressed in future investigations.
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Epidural electrical stimulation , Memantine , Neuromodulation , Prefrontal cortex , Radial maze , Working memory , Córtex pré-frontal , Estimulação elétrica epidural , Labirinto radial , Memantina , Memória operacional , Neuromodulação