Navegando por Autor "Hipólide, D. C."
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Apresentado em Evento Intrahippocampal aniracetam does not prevent contextual fear conditioning deficit induced by sleep deprivation(2011-08) Dubiela, F. P.; Queiroz, Claudio Marcos Teixeira de; Soares, J. C. K.; Tufik, S.; Hipólide, D. C.Objectives: The present work addressed whether deficits in fear conditioning (FC) performance observed after sleep deprivation (SD) (Behav Brain Res. 129:171, 2002) are dependent on AMPA receptor function and therefore could be prevent by local administration of the ampakine aniracetam. Methods and Results: Under deep anesthesia, stainless steel guide cannulae were bilaterally implanted in the dorsal hippocampal CA1 region of 3-month old male Wistar rats (250-300 g). After one week of recovery, animals were sleep deprived for 96 h by the modified multiple platform method (SD condition). Control animals remained in their home cages and were allowed to sleep ad lib. (CC condition). At the end of the sleep deprivation procedure, animals received bilateral infusions of vehicle, 0.1 or 1.0 M of aniracetam (1 µL) 15 min before the contextual fear conditioning training session. The behavioral paradigm consisted of 5 tone-shock pairings (60dB/5s, 0.6mA/1s) applied at intervals of 30 s. Twenty-four hours later, animals were exposed to a contextual FC test in the same environment where the FC training took place, followed by a tone FC test in a different apparatus where 5 tones were presented. Freezing behavior, defined as time spent in complete immobility, was recorded during all FC sessions and expressed as mean freezing duration / minute. Animals were divided into 6 groups (N=7-10), accordingly to the sleep deprivation procedure (CC, SD) and treatment (vehicle, aniracetam 0.1 M and 1.0 M). Contextual FC test: an one-way ANOVA indicated significant effect of group (p<0.05). Duncan post hoc analyses revealed that SD groups (SD vh: 8.0±2.4; SD ani 0.1M: 4.3±2.2; SD ani 1.0M: 7.9±4.6) displayed less freezing response in comparison to CC groups (CC vh: 31.3±2.7; CC ani 0.1M: 21.5±5.0; CC ani 1.0M: 31.9±3.9) (p<0.05) (values are mean±SEM in seconds). Tone FC test: A two-way repeated measures ANOVA indicated no significant main effects of group (p=0.10), a significant effect of minute (p<0.05), and no significant interaction between them (p=0.80). Duncan post hoc analyses revealed that all groups displayed an increased freezing response after the tone presentation (before tone: CC vh: 10.4±2.4; CC ani 0.1M: 8.0±1.6; CC ani 1.0M: 7.4±1.8; SD vh: 5.3±1.9; SD ani 0.1M: 2.7±1.8; SD ani 1.0M: 6.8±2.1; after tone: CC vh: 48.3±4.9; CC ani 0.1M: 47.3±3.5; CC ani 1.0M: 39.4±5.7; SD vh: 35.1±7.8; SD ani 0.1M: 35.5±6.9; SD ani 1.0M: 35.9±5.3) (p<0.05) (values are mean±SEM in seconds). Conclusions: Based on previous evidence showing a promnesic effects of aniracetam on the fear conditioning task (Brain Res. 768:197, 1997), we sought to verify whether intrahippocampal treatment with this drug could prevent learning deficits induced by sleep deprivation. Contrary to our hypothesis, aniracetam treatment did not affect fear conditioning performance of sleep deprived animals. This lack of effect might be due to hippocampal AMPA receptor downregulation after sleep deprivation.