Document Detail


Phasic and sustained fear are pharmacologically dissociable in rats.
MedLine Citation:
PMID:  21471958     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Previous findings suggest differences in the neuroanatomical substrates of short- (seconds) vs longer-duration (minutes) fear responses. We now report that phasic and sustained fear can also be differentiated pharmacologically, based on their response to several treatments that either are or are not clinically effective anxiolytics. For these experiments, short- or long-duration clicker stimuli were paired with footshock. Acoustic startle amplitude was later measured in the absence of the clicker, or within seconds (phasic fear) or minutes (sustained fear) of its onset. Before testing, rats received a single injection of vehicle, the benzodiazepine chlordiazepoxide, the 5HT(1A) agonist and dopamine D2 antagonist buspirone, the selective serotonin reuptake inhibitor fluoxetine, or a 3-week treatment with either vehicle or fluoxetine. Chlordiazepoxide blocked sustained, but not phasic startle increases. Acute buspirone, which is not anxiolytic in human beings, did not affect sustained startle increases, but did disrupt phasic increases. Chronic fluoxetine blocked sustained startle increases and unreliably reduced phasic increases; acute fluoxetine affected neither. The results indicate that phasic and sustained fear responses can be pharmacologically dissociated, further validating this distinction, and suggest that sustained startle increases may be especially useful as anxiety models and anxiolytic screens.
Authors:
Leigh Miles; Michael Davis; David Walker
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2011-04-06
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  36     ISSN:  1740-634X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-06-15     Completed Date:  2012-03-22     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  England    
Other Details:
Languages:  eng     Pagination:  1563-74     Citation Subset:  IM    
Affiliation:
Department of Molecular and Systems Pharmacology, Emory University, Atlanta, GA 30329, USA. amiles@emory.edu
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MeSH Terms
Descriptor/Qualifier:
Acoustic Stimulation / methods
Animals
Buspirone / pharmacology*
Chlordiazepoxide / pharmacology*
Conditioning (Psychology) / drug effects,  physiology
Fear / drug effects*,  physiology*,  psychology
Humans
Male
Models, Psychological
Rats
Rats, Sprague-Dawley
Startle Reaction / drug effects*,  physiology*
Time Factors
Grant Support
ID/Acronym/Agency:
MH080330/MH/NIMH NIH HHS; MH47840/MH/NIMH NIH HHS; R01 MH080330/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
36505-84-7/Buspirone; 58-25-3/Chlordiazepoxide
Comments/Corrections

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