Topiramate diminishes fear memory consolidation and extinguishes conditioned fear in rats

Topiramate diminishes fear memory consolidation and extinguishes conditioned fear in rats

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J Psychiatry Neurosci 2011;36(4):250-5

Pedro Antônio Schmidt do Prado-Lima, MD, PhD; Myriam Fortes Perrenoud, PhD; Christian Haag Kristensen, PhD; Martin Cammarota, MD, PhD; Ivan Izquierdo, MD, PhD

Prado-Lima, Perrenoud, Cammarota, Izquierdo — Centro de Memória, Instituto do Cérebro, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS); Prado-Lima — Laboratório de Neurociências, Instituto de Pesquisas Biomédicas, PUCRS; Kristensen — Grupo de Pesquisa Cognição, Emoção e Comportamento, Programa de Pós-Graduação em Psicologia, PUCRS, Porto Alegre, Brazil

Abstract

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: Topiramate diminishes fear memory consolidation and promotes extinction of inhibitory avoidance memory.


Submitted July 13, 2010; Revised Nov. 25, 2010; Accepted Dec. 16, 2010.

Competing interests: Dr. Prado-Lima declared having received travel support from Janssen-Cilag, Eli Lilly and Novartis, as well as consultancy and lecture fees from Wyeth. Dr. Kristensen declared having received travel assistance from Novartis. None declared for Drs. Perrenoud, Cammarota and Izquierdo.

Contributors: All authors helped design the study and approved the article for publication. Dr. Perrenoud acquired the data, which was analyzed by all other authors. Drs. Prado-Lima and Kristensen wrote the article, which Drs. Perrenoud, Cammarota and Izquierdo reviewed.

DOI: 10.1503/jpn.100115

Correspondence to: Dr. P.A. Prado-Lima, Rua Álvares Machado, 44/305, Porto Alegre, Brazil; paspl@uol.com.br