Repeated valproate treatment facilitates fear extinction under specific stimulus conditions

• Published in: Neuroscience letters 2013-09, Vol.552, p.108-113
• Main Authors: Heinrichs, Stephen C., Leite-Morris, Kimberly A., Rasmusson, Ann M., Kaplan, Gary B.
• Format: Article
• Language: English
• Subjects: Animals; Butyric Acid - pharmacology; Conditioned fear; Conditioning, Classical - drug effects; Extinction learning; Extinction, Psychological - drug effects; Fear - drug effects; Histone deacetylase inhibitors; Histone Deacetylase Inhibitors - pharmacology; Male; Mice; Mouse; Sodium butyrate; Time Factors; Valproate; Valproic Acid - pharmacology
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2013.07.035

•Studies of treatment effects of histone deacetylase inhibitors in fear extinction.•Freezing behaviors developed after six conditioning sessions in a single day.•Fear extinction was either completely or partially extinguished over 40 sessions.•Using complete extinction paradigm, histone deacetylase inhibitors had no effects.•Using partial extinction paradigm, valproate treatment enhanced fear extinction. Single dose treatment with histone deacetylase inhibitor (HDACi) agents has been shown to enhance extinction learning in rodent models under certain conditions. The present novel studies were designed to examine the effects of repeated HDACi treatment, with valproate or sodium butyrate, on the extinction of conditioned fear. In Experiments 1 and 2, short duration CS exposure (30s) in combination with vehicle administration progressively attenuated conditioned fear responses over 40 or more sessions. This effective extinction training was not augmented by HDACi treatments. In Experiment 3, we used a long duration CS exposure (120s) to weaken extinction training. With these extinction parameters, repeated valproate treatment substantially facilitated the acquisition and retention of fear extinction. Results of this study extend previous work suggesting that HDACi's have utility in augmenting the efficiency of fear extinction, although their apparent benefits are critically dependent upon specific parameters of extinction training.