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Article: 5-HT 2A receptor antagonism by MDL 11,939 during inescapable stress prevents subsequent exaggeration of acoustic startle response and reduced body weight in rats
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Title5-HT 2A receptor antagonism by MDL 11,939 during inescapable stress prevents subsequent exaggeration of acoustic startle response and reduced body weight in rats
 
AuthorsJiang, X2 3
Zhang, ZJ2
Zhang, S1
Gamble, EH2
Min Jia2
Ursano, RJ2 3
Li, H2 3
 
Keywords5-HT2A receptor
body weight
MDL 11,939
PTSD
startle
stress
 
Issue Date2011
 
PublisherSage Publications Ltd.. The Journal's web site is located at http://jop.sagepub.com
 
CitationJournal Of Psychopharmacology, 2011, v. 25 n. 2, p. 287-295 [How to Cite?]
DOI: http://dx.doi.org/10.1177/0269881109106911
 
AbstractActivation of central 5-HT 2A receptor signaling and its subsequent alterations have been implicated in the pathophysiological response to stress and the pathogenesis of stress-associated psychiatric disorders. To further examine the association between alterations in central 5-HT 2A receptor signaling and the occurrence of stress-induced psychiatric symptoms, the present study, utilizing a learned helplessness stress model in rats, determined whether 5-HT 2A receptor signaling blockade during stress could prevent the occurrence of stress-induced physical and behavioral abnormalities. Rats subjected to restraint/tail shock for three days developed long-lasting elevated acoustic startle response (ASR) and reduced body weight, compared to non-stressed control animals. However, administration of the selective 5-HT 2A receptor antagonist, MDL 11,939 (?-phenyl-1-(2- phenylethyl)-4-piperidinemethanol), 30 min prior to exposure of the animals to the stress protocol prevented the subsequent occurrence of elevated ASR and reduced body weight in a dose-dependent manner in stressed subjects. Administration of MDL 11,939 to the animals immediately after exposure to the stress protocol also prevented the occurrence of exaggerated ASR, but was not able to normalize body weight. These findings suggest a critical role of the central 5HT 2A receptor activation in developing the pathophysiology associated with elevated ASR and reduced body weight during stress. The differential effects of MDL 11,939 on startle response and body weight and its potential clinical significance are discussed. © The Author(s) 2011.
 
ISSN0269-8811
2013 Impact Factor: 2.806
2013 SCImago Journal Rankings: 1.556
 
DOIhttp://dx.doi.org/10.1177/0269881109106911
 
ISI Accession Number IDWOS:000286878400013
Funding AgencyGrant Number
DAMD17-00-1-0110
USUHSRO88DC
Henry M. Jackson Foundation
USUHS Center for the Study of Traumatic Stress
Funding Information:

We thank Drs Joseph McCabe, Thomas Cote, and Nelson Arispe for their comments on this manuscript. This work was supported by DAMD grant 17-00-1-0110 (to HL), USUHS grant RO88DC (to HL), a Henry M. Jackson Foundation Fellowship (to XJ), and the USUHS Center for the Study of Traumatic Stress.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorJiang, X
 
dc.contributor.authorZhang, ZJ
 
dc.contributor.authorZhang, S
 
dc.contributor.authorGamble, EH
 
dc.contributor.authorMin Jia
 
dc.contributor.authorUrsano, RJ
 
dc.contributor.authorLi, H
 
dc.date.accessioned2010-10-31T13:34:32Z
 
dc.date.available2010-10-31T13:34:32Z
 
dc.date.issued2011
 
dc.description.abstractActivation of central 5-HT 2A receptor signaling and its subsequent alterations have been implicated in the pathophysiological response to stress and the pathogenesis of stress-associated psychiatric disorders. To further examine the association between alterations in central 5-HT 2A receptor signaling and the occurrence of stress-induced psychiatric symptoms, the present study, utilizing a learned helplessness stress model in rats, determined whether 5-HT 2A receptor signaling blockade during stress could prevent the occurrence of stress-induced physical and behavioral abnormalities. Rats subjected to restraint/tail shock for three days developed long-lasting elevated acoustic startle response (ASR) and reduced body weight, compared to non-stressed control animals. However, administration of the selective 5-HT 2A receptor antagonist, MDL 11,939 (?-phenyl-1-(2- phenylethyl)-4-piperidinemethanol), 30 min prior to exposure of the animals to the stress protocol prevented the subsequent occurrence of elevated ASR and reduced body weight in a dose-dependent manner in stressed subjects. Administration of MDL 11,939 to the animals immediately after exposure to the stress protocol also prevented the occurrence of exaggerated ASR, but was not able to normalize body weight. These findings suggest a critical role of the central 5HT 2A receptor activation in developing the pathophysiology associated with elevated ASR and reduced body weight during stress. The differential effects of MDL 11,939 on startle response and body weight and its potential clinical significance are discussed. © The Author(s) 2011.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationJournal Of Psychopharmacology, 2011, v. 25 n. 2, p. 287-295 [How to Cite?]
DOI: http://dx.doi.org/10.1177/0269881109106911
 
dc.identifier.doihttp://dx.doi.org/10.1177/0269881109106911
 
dc.identifier.epage295
 
dc.identifier.hkuros174207
 
dc.identifier.isiWOS:000286878400013
Funding AgencyGrant Number
DAMD17-00-1-0110
USUHSRO88DC
Henry M. Jackson Foundation
USUHS Center for the Study of Traumatic Stress
Funding Information:

We thank Drs Joseph McCabe, Thomas Cote, and Nelson Arispe for their comments on this manuscript. This work was supported by DAMD grant 17-00-1-0110 (to HL), USUHS grant RO88DC (to HL), a Henry M. Jackson Foundation Fellowship (to XJ), and the USUHS Center for the Study of Traumatic Stress.

 
dc.identifier.issn0269-8811
2013 Impact Factor: 2.806
2013 SCImago Journal Rankings: 1.556
 
dc.identifier.issue2
 
dc.identifier.openurl
 
dc.identifier.pmid19889890
 
dc.identifier.scopuseid_2-s2.0-79551664836
 
dc.identifier.spage287
 
dc.identifier.urihttp://hdl.handle.net/10722/127593
 
dc.identifier.volume25
 
dc.languageeng
 
dc.publisherSage Publications Ltd.. The Journal's web site is located at http://jop.sagepub.com
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofJournal of Psychopharmacology
 
dc.relation.referencesReferences in Scopus
 
dc.rightsJournal of Psychopharmacology. Copyright © Sage Publications Ltd..
 
dc.subject.meshBody Weight - drug effects - physiology
 
dc.subject.meshHelplessness, Learned
 
dc.subject.meshPiperidines - pharmacology - therapeutic use
 
dc.subject.meshReceptor, Serotonin, 5-HT2A - physiology
 
dc.subject.meshStartle Reaction - drug effects - physiology
 
dc.subject5-HT2A receptor
 
dc.subjectbody weight
 
dc.subjectMDL 11,939
 
dc.subjectPTSD
 
dc.subjectstartle
 
dc.subjectstress
 
dc.title5-HT 2A receptor antagonism by MDL 11,939 during inescapable stress prevents subsequent exaggeration of acoustic startle response and reduced body weight in rats
 
dc.typeArticle
 
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Author Affiliations
  1. Wootton High School
  2. Center for the Study of Traumatic Stress
  3. Uniformed Services University of the Health Sciences