title: The Class I HDAC inhibitor RGFP963 enhances consolidation of cued fear extinction.
abstract: Evidence indicates that broad, nonspecific histone deacetylase (HDAC) inhibition enhances learning and memory, however, the contribution of the various HDACs to specific forms of learning is incompletely understood. Here, we show that the Class I HDAC inhibitor, RGFP963, enhances consolidation of cued fear extinction. However, RGFP966, a strong inhibitor of HDAC3, does not significantly enhance consolidation of cued fear extinction. These data extend previous evidence that demonstrate the Class I HDACs play a role in the consolidation of long-term memory, suggesting that HDAC1 and/or HDAC2, but less likely HDAC3, may function as negative regulators of extinction retention. The development of specific HDAC inhibitors, such as RGFP963, will further illuminate the role of specific HDACs in various types of learning and memory. Moreover, HDAC inhibitors that enhance cued fear extinction may show translational promise for the treatment of fear-related disorders, including post-traumatic stress disorder (PTSD).
authors.affiliation: Behavioral Neuroscience and Psychiatric Disorders, Emory University, Atlanta, Georgia 30329, USA.
authors.forename: Mallory E
authors.initials: ME
authors.lastname: Bowers
authors.affiliation: RepliGen Waltham, Massachusetts 02453, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Xia
authors.affiliation: RepliGen Waltham, Massachusetts 02453, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Carreiro
authors.affiliation: Behavioral Neuroscience and Psychiatric Disorders, Emory University, Atlanta, Georgia 30329, USA Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA kressle@emory.edu.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Ressler
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D003463:Cues; D005108:Extinction, Psychological / Q000187:drug effects* / Q000502:physiology; D005239:Fear / Q000187:drug effects* / Q000502:physiology; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects / Q000502:physiology; D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D056464:Histone Deacetylase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009483:Neuropsychological Tests; D000099186:Histone Deacetylase 3
chemical_list: D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D000099186:Histone Deacetylase 3; C484389:Hdac1 protein, mouse; C533424:Hdac2 protein, mouse