RESUMO
BACKGROUND: Topiramate has been recognized as a drug that can induce memory and cognitive impairment. Using the one-trial inhibitory avoidance task, we sought to verify the effect of topiramate on consolidation and extinction of aversive memory. Our hypothesis was that topiramate inhibits the consolidation and enhances the extinction of this fear memory. METHODS: In experiment 1, which occured immediately or 3 hours after training, topiramate was administered to rats, and consolidation of memory was verified 18 days after the conditioning session. In experiment 2, which occured 18-22 days after the training session, rats were submitted to the extinction protocol. Rats received topiramate 14 days before or during the extinction protocol. RESULTS: Topiramate blocked fear memory retention (p < 0.01) and enhanced fear memory extinction (p < 0.001) only when administered during the extinction protocol. LIMITATIONS: This experimental design did not allow us to determine whether topiramate also blocked the reconsolidation of fear memory. CONCLUSION: Topira mate diminishes fear memory consolidation and promotes extinction of inhibitory avoidance memory.
Assuntos
Condicionamento Psicológico/efeitos dos fármacos , Extinção Psicológica/efeitos dos fármacos , Medo/efeitos dos fármacos , Frutose/análogos & derivados , Memória/efeitos dos fármacos , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Frutose/farmacologia , Masculino , Ratos , Ratos Wistar , TopiramatoRESUMO
Thyroid hormones (THs) have a relevant action on brain development and maintenance. By using an acute treatment to induce a hyperthyroid animal model, we aimed at investigating the effect of an altered THs levels on learning and memory and on the activity of Na(+), K(+)-ATPase in the rat brain. Our results have shown that the acute treatment with L-T4 did not alter the retrieval of the inhibitory avoidance task, but had a significant effect on the elevated plus maze and on open-field performance in rats. We suggest that animals subjected to L-T4 administration improved the habituation to a novel environment as well as a better evaluation of a dangerous environment, respectively. Na(+), K(+)-ATPase activity is increased in parietal cortex (30%), but it is not altered in hippocampus in L-T4 treated group. These both brain structures are involved in memory processing and it was previously demonstrated that there is a double dissociation between them for spatial location information, perceptual and episodic memory. We propose the hypothesis that this increase of Na(+), K(+)-ATPase activity in parietal cortex may be correlated to our results in behavior tests, which suggest a role of THs as well as of the Na(+), K(+)-ATPase in the cognitive process.
Assuntos
Comportamento Animal/efeitos dos fármacos , Encéfalo/enzimologia , Habituação Psicofisiológica/efeitos dos fármacos , Memória/efeitos dos fármacos , Assunção de Riscos , ATPase Trocadora de Sódio-Potássio/metabolismo , Tiroxina/farmacologia , Animais , Ansiedade/psicologia , Aprendizagem da Esquiva/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/enzimologia , Masculino , Atividade Motora/efeitos dos fármacos , Lobo Parietal/efeitos dos fármacos , Lobo Parietal/enzimologia , Ratos , Ratos Wistar , Membranas Sinápticas/efeitos dos fármacos , Membranas Sinápticas/enzimologia , Hormônios Tireóideos/sangue , Tiroxina/sangueRESUMO
Thyroid hormones (THs), including triiodothyronine (T3) and tetraiodothyronine (T4), are recognized as key metabolic hormones of the body. THs are essential for normal maturation and function of the mammalian central nervous system (CNS) and its deficiency, during a critical period of development, profoundly affects cognitive function. Sodium-potassium adenosine 5'-triphosphatase (Na(+), K(+)-ATPase) is a crucial enzyme responsible for the active transport of sodium and potassium ions in the CNS necessary to maintain the ionic gradient for neuronal excitability. Studies suggest that Na(+), K(+)-ATPase might play a role on memory formation. Moreover, THs were proposed to stimulate Na(+), K(+)-ATPase activity in the heart of some species. In this work we investigated the effect of a chronic administration of L-thyroxine (L-T4) or propylthiouracil (PTU), an antithyroid drug, on some behavioral paradigms: inhibitory avoidance task, open field task, plus maze and Y-maze, and on the activity of Na(+), K(+)-ATPase in the rat parietal cortex and hippocampus. By using treatments which have shown to induce alterations in THs levels similar to those found in hyperthyroid and hypothyroid patients, we aimed to understand the effect of an altered hyperthyroid and hypothyroid state on learning and memory and on the activity of Na(+), K(+)-ATPase. Our results showed that a hyper and hypothyroid state can alter animal behavior and they also might indicate an effect of THs on learning and memory.