Effects of repeated treatment of phencyclidine on cognition and gene expression in C57BL/6 mice

A number of studies indicate that glutamatergic N-methyl-d-aspartate (NMDA) neurotransmission is disturbed in schizophrenia partly based on the findings that NMDA receptor antagonists such as phencyclidine (PCP) can reproduce a schizophrenia-like syndrome in both humans and rodents. This study inves...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:The international journal of neuropsychopharmacology 2009-03, Vol.12 (2), p.243-255
Hauptverfasser: Beraki, Simret, Diaz-Heijtz, Rochellys, Tai, Fadao, Ögren, Sven Ove
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 255
container_issue 2
container_start_page 243
container_title The international journal of neuropsychopharmacology
container_volume 12
creator Beraki, Simret
Diaz-Heijtz, Rochellys
Tai, Fadao
Ögren, Sven Ove
description A number of studies indicate that glutamatergic N-methyl-d-aspartate (NMDA) neurotransmission is disturbed in schizophrenia partly based on the findings that NMDA receptor antagonists such as phencyclidine (PCP) can reproduce a schizophrenia-like syndrome in both humans and rodents. This study investigated whether repeated administration of low doses of PCP can induce cognitive dysfunctions in mice at doses which produce no sensorimotor disturbances. In addition, the effects on cognition were related to the expression of two genes, Arc and spinophilin, which have been related to neuronal plasticity and learning. Adult male C57Bl/6J mice received daily s.c. doses of PCP (0.5–2.0 mg/kg) or saline for 7 d. Testing was performed 24 h after the last day of treatment. Only the 2.0 mg/kg PCP dose produced a consistent impairment in spatial learning and working memory performed in the water-maze task without any apparent sensorimotor deficits. Importantly, the 2.0 mg/kg PCP dose produced no impairment in a non-spatial learning paradigm in the water-maze task. PCP treatment altered Arc mRNA levels in the hippocampus and retrosplenial agranular cortex while leaving the striatum and prefrontal cortex unaffected. The mRNA expression of spinophilin was down-regulated in striatum by repeated PCP treatment. These results demonstrate that repeated treatment with low doses of PCP in mice can produce specific cognitive deficits which are associated with alterations in gene expression in brain regions that appear to play a role in the pathophysiology of schizophrenia. These results suggest that the low-dose PCP model may have significant potential in characterizing the behavioural and molecular mechanisms underlying cognitive deficits seen in schizophrenia patients.
doi_str_mv 10.1017/S1461145708009152
format Article
fullrecord <record><control><sourceid>proquest_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_562877</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><cupid>10_1017_S1461145708009152</cupid><sourcerecordid>20511307</sourcerecordid><originalsourceid>FETCH-LOGICAL-c598t-7ce23b4b44c6a3d18ddc24fff0dc98913a52ce62a05d690320fb8a381b55d183</originalsourceid><addsrcrecordid>eNqFkk1v1DAQhiMEop8_gAuKOHAL9fgrzhFWpSCt1AO9W449WVw2TrATQf89DhtYCVTVlxm9ft7xyDNF8QrIOyBQX30BLgG4qIkipAFBnxWnWWoqAQDPf-dQLfcnxVlK94RQLph8WZyAkoozDqeFvu46tFMqh66MOKKZ0JVTzLHHMC3q-BWDfbB773zAcgilHXbBTz5nJrhyh1nFn2PElBbNh3Ij6g_bK1n23uJF8aIz-4SXazwv7j5e320-Vdvbm8-b99vKikZNVW2Rspa3nFtpmAPlnKW86zribKMaYEZQi5IaIpxsCKOka5VhClohMs3Oi-pQNv3AcW71GH1v4oMejNer9C1nqIWkqq4z3zzKj3FwR9MfI4DilHNCsvftwZvB7zOmSfc-WdzvTcBhTlrKhikJ4kmQkjwnRpZu3vwD3g9zDPm_NM1HUUllhuAA2TikFLH72zQQvayD_m8dsuf1Wnhue3RHxzr_DLC1qOnb6N0Oj08_XvYXhN2-8Q</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>222282626</pqid></control><display><type>article</type><title>Effects of repeated treatment of phencyclidine on cognition and gene expression in C57BL/6 mice</title><source>MEDLINE</source><source>Access via Oxford University Press (Open Access Collection)</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Beraki, Simret ; Diaz-Heijtz, Rochellys ; Tai, Fadao ; Ögren, Sven Ove</creator><creatorcontrib>Beraki, Simret ; Diaz-Heijtz, Rochellys ; Tai, Fadao ; Ögren, Sven Ove</creatorcontrib><description>A number of studies indicate that glutamatergic N-methyl-d-aspartate (NMDA) neurotransmission is disturbed in schizophrenia partly based on the findings that NMDA receptor antagonists such as phencyclidine (PCP) can reproduce a schizophrenia-like syndrome in both humans and rodents. This study investigated whether repeated administration of low doses of PCP can induce cognitive dysfunctions in mice at doses which produce no sensorimotor disturbances. In addition, the effects on cognition were related to the expression of two genes, Arc and spinophilin, which have been related to neuronal plasticity and learning. Adult male C57Bl/6J mice received daily s.c. doses of PCP (0.5–2.0 mg/kg) or saline for 7 d. Testing was performed 24 h after the last day of treatment. Only the 2.0 mg/kg PCP dose produced a consistent impairment in spatial learning and working memory performed in the water-maze task without any apparent sensorimotor deficits. Importantly, the 2.0 mg/kg PCP dose produced no impairment in a non-spatial learning paradigm in the water-maze task. PCP treatment altered Arc mRNA levels in the hippocampus and retrosplenial agranular cortex while leaving the striatum and prefrontal cortex unaffected. The mRNA expression of spinophilin was down-regulated in striatum by repeated PCP treatment. These results demonstrate that repeated treatment with low doses of PCP in mice can produce specific cognitive deficits which are associated with alterations in gene expression in brain regions that appear to play a role in the pathophysiology of schizophrenia. These results suggest that the low-dose PCP model may have significant potential in characterizing the behavioural and molecular mechanisms underlying cognitive deficits seen in schizophrenia patients.</description><identifier>ISSN: 1461-1457</identifier><identifier>ISSN: 1469-5111</identifier><identifier>EISSN: 1469-5111</identifier><identifier>DOI: 10.1017/S1461145708009152</identifier><identifier>PMID: 18684341</identifier><language>eng</language><publisher>Cambridge, UK: Cambridge University Press</publisher><subject>Analysis of Variance ; Animals ; Behavior, Animal - drug effects ; Cognition - drug effects ; Cytoskeletal Proteins - genetics ; Cytoskeletal Proteins - metabolism ; Dose-Response Relationship, Drug ; Gene Expression Regulation - drug effects ; Hallucinogens - pharmacology ; Hippocampus - drug effects ; Hippocampus - metabolism ; Male ; Maze Learning - drug effects ; Medicin och hälsovetenskap ; Memory, Short-Term - drug effects ; Mice ; Mice, Inbred C57BL ; Microfilament Proteins - genetics ; Microfilament Proteins - metabolism ; Motor Activity - drug effects ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; Phencyclidine - pharmacology ; Rotarod Performance Test - methods ; Spatial Behavior - drug effects</subject><ispartof>The international journal of neuropsychopharmacology, 2009-03, Vol.12 (2), p.243-255</ispartof><rights>Copyright © 2008 CINP</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c598t-7ce23b4b44c6a3d18ddc24fff0dc98913a52ce62a05d690320fb8a381b55d183</citedby><cites>FETCH-LOGICAL-c598t-7ce23b4b44c6a3d18ddc24fff0dc98913a52ce62a05d690320fb8a381b55d183</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18684341$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:118424400$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Beraki, Simret</creatorcontrib><creatorcontrib>Diaz-Heijtz, Rochellys</creatorcontrib><creatorcontrib>Tai, Fadao</creatorcontrib><creatorcontrib>Ögren, Sven Ove</creatorcontrib><title>Effects of repeated treatment of phencyclidine on cognition and gene expression in C57BL/6 mice</title><title>The international journal of neuropsychopharmacology</title><addtitle>Int J Neuropsychopharmacol</addtitle><description>A number of studies indicate that glutamatergic N-methyl-d-aspartate (NMDA) neurotransmission is disturbed in schizophrenia partly based on the findings that NMDA receptor antagonists such as phencyclidine (PCP) can reproduce a schizophrenia-like syndrome in both humans and rodents. This study investigated whether repeated administration of low doses of PCP can induce cognitive dysfunctions in mice at doses which produce no sensorimotor disturbances. In addition, the effects on cognition were related to the expression of two genes, Arc and spinophilin, which have been related to neuronal plasticity and learning. Adult male C57Bl/6J mice received daily s.c. doses of PCP (0.5–2.0 mg/kg) or saline for 7 d. Testing was performed 24 h after the last day of treatment. Only the 2.0 mg/kg PCP dose produced a consistent impairment in spatial learning and working memory performed in the water-maze task without any apparent sensorimotor deficits. Importantly, the 2.0 mg/kg PCP dose produced no impairment in a non-spatial learning paradigm in the water-maze task. PCP treatment altered Arc mRNA levels in the hippocampus and retrosplenial agranular cortex while leaving the striatum and prefrontal cortex unaffected. The mRNA expression of spinophilin was down-regulated in striatum by repeated PCP treatment. These results demonstrate that repeated treatment with low doses of PCP in mice can produce specific cognitive deficits which are associated with alterations in gene expression in brain regions that appear to play a role in the pathophysiology of schizophrenia. These results suggest that the low-dose PCP model may have significant potential in characterizing the behavioural and molecular mechanisms underlying cognitive deficits seen in schizophrenia patients.</description><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Behavior, Animal - drug effects</subject><subject>Cognition - drug effects</subject><subject>Cytoskeletal Proteins - genetics</subject><subject>Cytoskeletal Proteins - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Hallucinogens - pharmacology</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - metabolism</subject><subject>Male</subject><subject>Maze Learning - drug effects</subject><subject>Medicin och hälsovetenskap</subject><subject>Memory, Short-Term - drug effects</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microfilament Proteins - genetics</subject><subject>Microfilament Proteins - metabolism</subject><subject>Motor Activity - drug effects</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Phencyclidine - pharmacology</subject><subject>Rotarod Performance Test - methods</subject><subject>Spatial Behavior - drug effects</subject><issn>1461-1457</issn><issn>1469-5111</issn><issn>1469-5111</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkk1v1DAQhiMEop8_gAuKOHAL9fgrzhFWpSCt1AO9W449WVw2TrATQf89DhtYCVTVlxm9ft7xyDNF8QrIOyBQX30BLgG4qIkipAFBnxWnWWoqAQDPf-dQLfcnxVlK94RQLph8WZyAkoozDqeFvu46tFMqh66MOKKZ0JVTzLHHMC3q-BWDfbB773zAcgilHXbBTz5nJrhyh1nFn2PElBbNh3Ij6g_bK1n23uJF8aIz-4SXazwv7j5e320-Vdvbm8-b99vKikZNVW2Rspa3nFtpmAPlnKW86zribKMaYEZQi5IaIpxsCKOka5VhClohMs3Oi-pQNv3AcW71GH1v4oMejNer9C1nqIWkqq4z3zzKj3FwR9MfI4DilHNCsvftwZvB7zOmSfc-WdzvTcBhTlrKhikJ4kmQkjwnRpZu3vwD3g9zDPm_NM1HUUllhuAA2TikFLH72zQQvayD_m8dsuf1Wnhue3RHxzr_DLC1qOnb6N0Oj08_XvYXhN2-8Q</recordid><startdate>20090301</startdate><enddate>20090301</enddate><creator>Beraki, Simret</creator><creator>Diaz-Heijtz, Rochellys</creator><creator>Tai, Fadao</creator><creator>Ögren, Sven Ove</creator><general>Cambridge University Press</general><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope></search><sort><creationdate>20090301</creationdate><title>Effects of repeated treatment of phencyclidine on cognition and gene expression in C57BL/6 mice</title><author>Beraki, Simret ; Diaz-Heijtz, Rochellys ; Tai, Fadao ; Ögren, Sven Ove</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c598t-7ce23b4b44c6a3d18ddc24fff0dc98913a52ce62a05d690320fb8a381b55d183</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Behavior, Animal - drug effects</topic><topic>Cognition - drug effects</topic><topic>Cytoskeletal Proteins - genetics</topic><topic>Cytoskeletal Proteins - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Hallucinogens - pharmacology</topic><topic>Hippocampus - drug effects</topic><topic>Hippocampus - metabolism</topic><topic>Male</topic><topic>Maze Learning - drug effects</topic><topic>Medicin och hälsovetenskap</topic><topic>Memory, Short-Term - drug effects</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microfilament Proteins - genetics</topic><topic>Microfilament Proteins - metabolism</topic><topic>Motor Activity - drug effects</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Phencyclidine - pharmacology</topic><topic>Rotarod Performance Test - methods</topic><topic>Spatial Behavior - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Beraki, Simret</creatorcontrib><creatorcontrib>Diaz-Heijtz, Rochellys</creatorcontrib><creatorcontrib>Tai, Fadao</creatorcontrib><creatorcontrib>Ögren, Sven Ove</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><jtitle>The international journal of neuropsychopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Beraki, Simret</au><au>Diaz-Heijtz, Rochellys</au><au>Tai, Fadao</au><au>Ögren, Sven Ove</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of repeated treatment of phencyclidine on cognition and gene expression in C57BL/6 mice</atitle><jtitle>The international journal of neuropsychopharmacology</jtitle><addtitle>Int J Neuropsychopharmacol</addtitle><date>2009-03-01</date><risdate>2009</risdate><volume>12</volume><issue>2</issue><spage>243</spage><epage>255</epage><pages>243-255</pages><issn>1461-1457</issn><issn>1469-5111</issn><eissn>1469-5111</eissn><abstract>A number of studies indicate that glutamatergic N-methyl-d-aspartate (NMDA) neurotransmission is disturbed in schizophrenia partly based on the findings that NMDA receptor antagonists such as phencyclidine (PCP) can reproduce a schizophrenia-like syndrome in both humans and rodents. This study investigated whether repeated administration of low doses of PCP can induce cognitive dysfunctions in mice at doses which produce no sensorimotor disturbances. In addition, the effects on cognition were related to the expression of two genes, Arc and spinophilin, which have been related to neuronal plasticity and learning. Adult male C57Bl/6J mice received daily s.c. doses of PCP (0.5–2.0 mg/kg) or saline for 7 d. Testing was performed 24 h after the last day of treatment. Only the 2.0 mg/kg PCP dose produced a consistent impairment in spatial learning and working memory performed in the water-maze task without any apparent sensorimotor deficits. Importantly, the 2.0 mg/kg PCP dose produced no impairment in a non-spatial learning paradigm in the water-maze task. PCP treatment altered Arc mRNA levels in the hippocampus and retrosplenial agranular cortex while leaving the striatum and prefrontal cortex unaffected. The mRNA expression of spinophilin was down-regulated in striatum by repeated PCP treatment. These results demonstrate that repeated treatment with low doses of PCP in mice can produce specific cognitive deficits which are associated with alterations in gene expression in brain regions that appear to play a role in the pathophysiology of schizophrenia. These results suggest that the low-dose PCP model may have significant potential in characterizing the behavioural and molecular mechanisms underlying cognitive deficits seen in schizophrenia patients.</abstract><cop>Cambridge, UK</cop><pub>Cambridge University Press</pub><pmid>18684341</pmid><doi>10.1017/S1461145708009152</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1461-1457
ispartof The international journal of neuropsychopharmacology, 2009-03, Vol.12 (2), p.243-255
issn 1461-1457
1469-5111
1469-5111
language eng
recordid cdi_swepub_primary_oai_swepub_ki_se_562877
source MEDLINE; Access via Oxford University Press (Open Access Collection); EZB-FREE-00999 freely available EZB journals
subjects Analysis of Variance
Animals
Behavior, Animal - drug effects
Cognition - drug effects
Cytoskeletal Proteins - genetics
Cytoskeletal Proteins - metabolism
Dose-Response Relationship, Drug
Gene Expression Regulation - drug effects
Hallucinogens - pharmacology
Hippocampus - drug effects
Hippocampus - metabolism
Male
Maze Learning - drug effects
Medicin och hälsovetenskap
Memory, Short-Term - drug effects
Mice
Mice, Inbred C57BL
Microfilament Proteins - genetics
Microfilament Proteins - metabolism
Motor Activity - drug effects
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Phencyclidine - pharmacology
Rotarod Performance Test - methods
Spatial Behavior - drug effects
title Effects of repeated treatment of phencyclidine on cognition and gene expression in C57BL/6 mice
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T13%3A09%3A59IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Effects%20of%20repeated%20treatment%20of%20phencyclidine%20on%20cognition%20and%20gene%20expression%20in%20C57BL/6%20mice&rft.jtitle=The%20international%20journal%20of%20neuropsychopharmacology&rft.au=Beraki,%20Simret&rft.date=2009-03-01&rft.volume=12&rft.issue=2&rft.spage=243&rft.epage=255&rft.pages=243-255&rft.issn=1461-1457&rft.eissn=1469-5111&rft_id=info:doi/10.1017/S1461145708009152&rft_dat=%3Cproquest_swepu%3E20511307%3C/proquest_swepu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=222282626&rft_id=info:pmid/18684341&rft_cupid=10_1017_S1461145708009152&rfr_iscdi=true