PMID- 24646280
OWN - NLM
STAT- MEDLINE
DCOM- 20150605
LR  - 20220317
IS  - 1470-8752 (Electronic)
IS  - 0300-5127 (Print)
IS  - 0300-5127 (Linking)
VI  - 42
IP  - 2
DP  - 2014 Apr
TI  - HDAC inhibitors as cognitive enhancers in fear, anxiety and trauma therapy: where 
      do we stand?
PG  - 569-81
LID - 10.1042/BST20130233 [doi]
AB  - A novel strategy to treat anxiety and fear-related disorders such as phobias, 
      panic and PTSD (post-traumatic stress disorder) is combining CBT (cognitive 
      behavioural therapy), including extinction-based exposure therapy, with cognitive 
      enhancers. By targeting and boosting mechanisms underlying learning, drug 
      development in this field aims at designing CBT-augmenting compounds that help to 
      overcome extinction learning deficits, promote long-term fear inhibition and thus 
      support relapse prevention. Progress in revealing the role of epigenetic 
      regulation of specific genes associated with extinction memory generation has 
      opened new avenues in this direction. The present review examines recent evidence 
      from pre-clinical studies showing that increasing histone acetylation, either via 
      genetic or pharmacological inhibition of HDACs (histone deacetylases) by e.g. 
      vorinostat/SAHA (suberoylanilide hydroxamic acid), entinostat/MS-275, sodium 
      butyrate, TSA (trichostatin A) or VPA (valproic acid), or by targeting HATs 
      (histone acetyltransferases), augments fear extinction and, importantly, 
      generates a long-term extinction memory that can protect from return of fear 
      phenomena. The molecular mechanisms and pathways involved including BDNF 
      (brain-derived neurotrophic factor) and NMDA (N-methyl-D-aspartate) receptor 
      signalling are just beginning to be revealed. First studies in healthy humans are 
      in support of extinction-facilitating effects of HDAC inhibitors. Very recent 
      evidence that HDAC inhibitors can rescue deficits in extinction-memory-impaired 
      rodents indicates a potential clinical utility of this approach also for exposure 
      therapy-resistant patients. Important future work includes investigation of the 
      long-term safety aspects of HDAC inhibitor treatment, as well as design of 
      isotype(s)-specific inhibitors. Taken together, HDAC inhibitors display promising 
      potential as pharmacological adjuncts to augment the efficacy of exposure-based 
      approaches in anxiety and trauma therapy.
FAU - Whittle, Nigel
AU  - Whittle N
AD  - *Department of Pharmacology and Toxicology, Institute of Pharmacy and Center for 
      Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 
      80-82/III, A-6020 Innsbruck, Austria.
FAU - Singewald, Nicolas
AU  - Singewald N
AD  - *Department of Pharmacology and Toxicology, Institute of Pharmacy and Center for 
      Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 
      80-82/III, A-6020 Innsbruck, Austria.
LA  - eng
GR  - P 25375/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Biochem Soc Trans
JT  - Biochemical Society transactions
JID - 7506897
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Nootropic Agents)
SB  - IM
MH  - Anxiety/*drug therapy
MH  - Fear/*drug effects
MH  - Histone Deacetylase Inhibitors/*therapeutic use
MH  - Humans
MH  - Nootropic Agents/*therapeutic use
MH  - Wounds and Injuries/drug therapy
PMC - PMC3961057
EDAT- 2014/03/22 06:00
MHDA- 2015/06/06 06:00
PMCR- 2014/03/20
CRDT- 2014/03/21 06:00
PHST- 2014/03/21 06:00 [entrez]
PHST- 2014/03/22 06:00 [pubmed]
PHST- 2015/06/06 06:00 [medline]
PHST- 2014/03/20 00:00 [pmc-release]
AID - BST20130233 [pii]
AID - 10.1042/BST20130233 [doi]
PST - ppublish
SO  - Biochem Soc Trans. 2014 Apr;42(2):569-81. doi: 10.1042/BST20130233.