title: Repeated valproate treatment facilitates fear extinction under specific stimulus conditions.
abstract: 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 (120 s) 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.
authors.affiliation: Research Service, VA Boston Healthcare System, Boston, MA, USA.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Heinrichs
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Leite-Morris
authors.forename: Ann M
authors.initials: AM
authors.lastname: Rasmusson
authors.forename: Gary B
authors.initials: GB
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D020148:Butyric Acid / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects*; D005239:Fear / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D013997:Time Factors; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D056572:Histone Deacetylase Inhibitors; D020148:Butyric Acid; D014635:Valproic Acid
keywords: Conditioned fear; Extinction learning; HDAC; HDACi; Histone deacetylase inhibitors; Mouse; PTSD; SB; Sodium butyrate; VPA; Valproate; histone deacetylase; histone deacetylase inhibitor; post-traumatic stress disorder; sodium butyrate; valproic acid