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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

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
Authors
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
Citation
Journal Of Psychopharmacology, 2011, v. 25 n. 2, p. 287-295 How to Cite?
Abstract
Activation 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.
Persistent Identifierhttp://hdl.handle.net/10722/127593
ISSN
2013 Impact Factor: 2.806
2013 SCImago Journal Rankings: 1.556
ISI Accession Number ID
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.

References

 

Author Affiliations
  1. Wootton High School
  2. Center for the Study of Traumatic Stress
  3. Uniformed Services University of the Health Sciences
DC FieldValueLanguage
dc.contributor.authorJiang, Xen_HK
dc.contributor.authorZhang, ZJen_HK
dc.contributor.authorZhang, Sen_HK
dc.contributor.authorGamble, EHen_HK
dc.contributor.authorMin Jiaen_HK
dc.contributor.authorUrsano, RJen_HK
dc.contributor.authorLi, Hen_HK
dc.date.accessioned2010-10-31T13:34:32Z-
dc.date.available2010-10-31T13:34:32Z-
dc.date.issued2011en_HK
dc.identifier.citationJournal Of Psychopharmacology, 2011, v. 25 n. 2, p. 287-295en_HK
dc.identifier.issn0269-8811en_HK
dc.identifier.urihttp://hdl.handle.net/10722/127593-
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.en_HK
dc.languageengen_HK
dc.publisherSage Publications Ltd.. The Journal's web site is located at http://jop.sagepub.comen_HK
dc.relation.ispartofJournal of Psychopharmacologyen_HK
dc.rightsJournal of Psychopharmacology. Copyright © Sage Publications Ltd..-
dc.subject5-HT2A receptoren_HK
dc.subjectbody weighten_HK
dc.subjectMDL 11,939en_HK
dc.subjectPTSDen_HK
dc.subjectstartleen_HK
dc.subjectstressen_HK
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.title5-HT 2A receptor antagonism by MDL 11,939 during inescapable stress prevents subsequent exaggeration of acoustic startle response and reduced body weight in ratsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0269-8811&volume=25&issue=2&spage=289&epage=297&date=2009&atitle=5-HT2A+receptor+antagonism+by+MDL+11,939+during+inescapable+stress+prevents+subsequent+exaggeration+of+acoustic+startle+response+and+reduced+body+weight+in+rats-
dc.identifier.emailZhang, ZJ: zhangzj@hkucc.hku.hken_HK
dc.identifier.authorityZhang, ZJ=rp01297en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1177/0269881109106911en_HK
dc.identifier.pmid19889890en_US
dc.identifier.scopuseid_2-s2.0-79551664836en_HK
dc.identifier.hkuros174207en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79551664836&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume25en_HK
dc.identifier.issue2en_HK
dc.identifier.spage287en_HK
dc.identifier.epage295en_HK
dc.identifier.isiWOS:000286878400013-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridJiang, X=7404627223en_HK
dc.identifier.scopusauthoridZhang, ZJ=8061473900en_HK
dc.identifier.scopusauthoridZhang, S=37007255200en_HK
dc.identifier.scopusauthoridGamble, EH=7004004411en_HK
dc.identifier.scopusauthoridMin Jia=37006669700en_HK
dc.identifier.scopusauthoridUrsano, RJ=7005305249en_HK
dc.identifier.scopusauthoridLi, H=36934013100en_HK

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