Amphetamine sensitization impairs cognition and reduces dopamine turnover in primate prefrontal cortex
Amphetamine (AMPH) sensitization in monkeys produces long-lasting behavioral changes that model positive (hallucinatory-like behaviors) and negative (psychomotor depression) symptoms of schizophrenia. The extent to which this model produces the core deficit in schizophrenia—working memory impairment...
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| Veröffentlicht in: | Biological psychiatry (1969) 2005-04, Vol.57 (7), p.743-751 |
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| creator | Castner, Stacy A. Vosler, Peter S. Goldman-Rakic, Patricia S. |
| description | Amphetamine (AMPH) sensitization in monkeys produces long-lasting behavioral changes that model positive (hallucinatory-like behaviors) and negative (psychomotor depression) symptoms of schizophrenia. The extent to which this model produces the core deficit in schizophrenia—working memory impairment—is unknown.
Two groups of rhesus monkeys were sensitized to AMPH over 6 weeks. In one group, acquisition of cognitive tasks (delayed response, visual discrimination, delayed nonmatch-to-sample) was examined beginning 6+ months postsensitization. The second group was pretrained to stability on delayed response before sensitization. Regional postmortem concentrations of dopamine and its metabolites were examined in tissue from age-matched AMPH-naïve and AMPH-sensitized monkeys using high-performance liquid chromatography with electrochemical detection (HPLC-ECD).
The AMPH-sensitized monkeys were profoundly impaired in their ability to acquire cognitive tasks compared with AMPH-naïve monkeys. Pretrained monkeys showed impaired delayed response performance for several months following sensitization. Analysis by HPLC revealed that AMPH sensitization significantly reduced dopamine turnover in prefrontal cortex and striatum.
Impairments in the acquisition and performance of spatial delayed response in association with reduced dopamine turnover in prefrontal cortex following AMPH sensitization provide further support for the relevance of this model to both the etiology and the treatment of cognitive dysfunction in schizophrenia. |
| doi_str_mv | 10.1016/j.biopsych.2004.12.019 |
| format | Article |
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Two groups of rhesus monkeys were sensitized to AMPH over 6 weeks. In one group, acquisition of cognitive tasks (delayed response, visual discrimination, delayed nonmatch-to-sample) was examined beginning 6+ months postsensitization. The second group was pretrained to stability on delayed response before sensitization. Regional postmortem concentrations of dopamine and its metabolites were examined in tissue from age-matched AMPH-naïve and AMPH-sensitized monkeys using high-performance liquid chromatography with electrochemical detection (HPLC-ECD).
The AMPH-sensitized monkeys were profoundly impaired in their ability to acquire cognitive tasks compared with AMPH-naïve monkeys. Pretrained monkeys showed impaired delayed response performance for several months following sensitization. Analysis by HPLC revealed that AMPH sensitization significantly reduced dopamine turnover in prefrontal cortex and striatum.
Impairments in the acquisition and performance of spatial delayed response in association with reduced dopamine turnover in prefrontal cortex following AMPH sensitization provide further support for the relevance of this model to both the etiology and the treatment of cognitive dysfunction in schizophrenia.</description><identifier>ISSN: 0006-3223</identifier><identifier>EISSN: 1873-2402</identifier><identifier>DOI: 10.1016/j.biopsych.2004.12.019</identifier><identifier>PMID: 15820231</identifier><identifier>CODEN: BIPCBF</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>3,4-Dihydroxyphenylacetic Acid - metabolism ; Adult and adolescent clinical studies ; Amphetamine - adverse effects ; Amphetamine - pharmacology ; Analysis of Variance ; Animals ; Behavior, Animal - drug effects ; Behavioral psychophysiology ; Behavioral sensitization ; Biological and medical sciences ; Central Nervous System Stimulants - adverse effects ; Central Nervous System Stimulants - pharmacology ; Chromatography, High Pressure Liquid - methods ; Cognition Disorders - chemically induced ; Cognition Disorders - physiopathology ; Corpus Striatum - metabolism ; Discrimination Learning - drug effects ; Dopamine - metabolism ; dopamine transmission ; dorsolateral prefrontal cortex ; Electrochemistry - methods ; Female ; Fundamental and applied biological sciences. Psychology ; Homovanillic Acid - metabolism ; Macaca mulatta ; Male ; Medical sciences ; Neuropsychological Tests - statistics & numerical data ; Neurotransmission and behavior ; nonhuman primate ; Prefrontal Cortex - drug effects ; Prefrontal Cortex - metabolism ; Prefrontal Cortex - physiopathology ; Psychology. Psychoanalysis. Psychiatry ; Psychology. Psychophysiology ; Psychopathology. Psychiatry ; Psychoses ; Reaction Time - drug effects ; Reward ; Schizophrenia ; spatial working memory ; Time Factors ; Visual Perception - drug effects</subject><ispartof>Biological psychiatry (1969), 2005-04, Vol.57 (7), p.743-751</ispartof><rights>2005 Society of Biological Psychiatry</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c427t-557476ae3464f5f53603e74e87be2a1e56f2fbb18c0d90c8589ddb1f6ab859273</citedby><cites>FETCH-LOGICAL-c427t-557476ae3464f5f53603e74e87be2a1e56f2fbb18c0d90c8589ddb1f6ab859273</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.biopsych.2004.12.019$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16733214$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15820231$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Castner, Stacy A.</creatorcontrib><creatorcontrib>Vosler, Peter S.</creatorcontrib><creatorcontrib>Goldman-Rakic, Patricia S.</creatorcontrib><title>Amphetamine sensitization impairs cognition and reduces dopamine turnover in primate prefrontal cortex</title><title>Biological psychiatry (1969)</title><addtitle>Biol Psychiatry</addtitle><description>Amphetamine (AMPH) sensitization in monkeys produces long-lasting behavioral changes that model positive (hallucinatory-like behaviors) and negative (psychomotor depression) symptoms of schizophrenia. The extent to which this model produces the core deficit in schizophrenia—working memory impairment—is unknown.
Two groups of rhesus monkeys were sensitized to AMPH over 6 weeks. In one group, acquisition of cognitive tasks (delayed response, visual discrimination, delayed nonmatch-to-sample) was examined beginning 6+ months postsensitization. The second group was pretrained to stability on delayed response before sensitization. Regional postmortem concentrations of dopamine and its metabolites were examined in tissue from age-matched AMPH-naïve and AMPH-sensitized monkeys using high-performance liquid chromatography with electrochemical detection (HPLC-ECD).
The AMPH-sensitized monkeys were profoundly impaired in their ability to acquire cognitive tasks compared with AMPH-naïve monkeys. Pretrained monkeys showed impaired delayed response performance for several months following sensitization. Analysis by HPLC revealed that AMPH sensitization significantly reduced dopamine turnover in prefrontal cortex and striatum.
Impairments in the acquisition and performance of spatial delayed response in association with reduced dopamine turnover in prefrontal cortex following AMPH sensitization provide further support for the relevance of this model to both the etiology and the treatment of cognitive dysfunction in schizophrenia.</description><subject>3,4-Dihydroxyphenylacetic Acid - metabolism</subject><subject>Adult and adolescent clinical studies</subject><subject>Amphetamine - adverse effects</subject><subject>Amphetamine - pharmacology</subject><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Behavior, Animal - drug effects</subject><subject>Behavioral psychophysiology</subject><subject>Behavioral sensitization</subject><subject>Biological and medical sciences</subject><subject>Central Nervous System Stimulants - adverse effects</subject><subject>Central Nervous System Stimulants - pharmacology</subject><subject>Chromatography, High Pressure Liquid - methods</subject><subject>Cognition Disorders - chemically induced</subject><subject>Cognition Disorders - physiopathology</subject><subject>Corpus Striatum - metabolism</subject><subject>Discrimination Learning - drug effects</subject><subject>Dopamine - metabolism</subject><subject>dopamine transmission</subject><subject>dorsolateral prefrontal cortex</subject><subject>Electrochemistry - methods</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Homovanillic Acid - metabolism</subject><subject>Macaca mulatta</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Neuropsychological Tests - statistics & numerical data</subject><subject>Neurotransmission and behavior</subject><subject>nonhuman primate</subject><subject>Prefrontal Cortex - drug effects</subject><subject>Prefrontal Cortex - metabolism</subject><subject>Prefrontal Cortex - physiopathology</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychology. Psychophysiology</subject><subject>Psychopathology. Psychiatry</subject><subject>Psychoses</subject><subject>Reaction Time - drug effects</subject><subject>Reward</subject><subject>Schizophrenia</subject><subject>spatial working memory</subject><subject>Time Factors</subject><subject>Visual Perception - drug effects</subject><issn>0006-3223</issn><issn>1873-2402</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMtu1TAURS0EorePX6gygVmCH7GdzKgqoEiVOiljy7GPqa8SO9hORfl63N6LOmR0dKy1j7cWQpcEdwQT8WnfTT6u-ck8dBTjviO0w2R8g3ZkkKylPaZv0Q5jLFpGKTtBpznv6yopJe_RCeEDxZSRHXJXy_oARS8-QJMhZF_8H118DI1fVu1Tbkz8GfzLiw62SWA3A7mxcT2EypZCfITU-NCsyS-6QJ3gUgxFzzWdCvw-R--cnjNcHOcZ-vH1y_31TXt79-379dVta3oqS8u57KXQwHrRO-44E5iB7GGQE1BNgAtH3TSRwWA7YjPwYbR2Ik7oaeAjlewMfTzcXVP8tUEuavHZwDzrAHHLikhG2TjwCooDaFLMudZVL93TkyJYPRtWe_XPsHo2rAhV1XANXh5_2KYF7GvsqLQCH46AzkbPLulgfH7lhGSMkr5ynw8cVB-PHpLKxkMwYH0CU5SN_n9d_gLTiZ-j</recordid><startdate>20050401</startdate><enddate>20050401</enddate><creator>Castner, Stacy A.</creator><creator>Vosler, Peter S.</creator><creator>Goldman-Rakic, Patricia S.</creator><general>Elsevier Inc</general><general>Elsevier Science</general><scope>IQODW</scope><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>7TK</scope></search><sort><creationdate>20050401</creationdate><title>Amphetamine sensitization impairs cognition and reduces dopamine turnover in primate prefrontal cortex</title><author>Castner, Stacy A. ; Vosler, Peter S. ; Goldman-Rakic, Patricia S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c427t-557476ae3464f5f53603e74e87be2a1e56f2fbb18c0d90c8589ddb1f6ab859273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>3,4-Dihydroxyphenylacetic Acid - metabolism</topic><topic>Adult and adolescent clinical studies</topic><topic>Amphetamine - adverse effects</topic><topic>Amphetamine - pharmacology</topic><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Behavior, Animal - drug effects</topic><topic>Behavioral psychophysiology</topic><topic>Behavioral sensitization</topic><topic>Biological and medical sciences</topic><topic>Central Nervous System Stimulants - adverse effects</topic><topic>Central Nervous System Stimulants - pharmacology</topic><topic>Chromatography, High Pressure Liquid - methods</topic><topic>Cognition Disorders - chemically induced</topic><topic>Cognition Disorders - physiopathology</topic><topic>Corpus Striatum - metabolism</topic><topic>Discrimination Learning - drug effects</topic><topic>Dopamine - metabolism</topic><topic>dopamine transmission</topic><topic>dorsolateral prefrontal cortex</topic><topic>Electrochemistry - methods</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Homovanillic Acid - metabolism</topic><topic>Macaca mulatta</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neuropsychological Tests - statistics & numerical data</topic><topic>Neurotransmission and behavior</topic><topic>nonhuman primate</topic><topic>Prefrontal Cortex - drug effects</topic><topic>Prefrontal Cortex - metabolism</topic><topic>Prefrontal Cortex - physiopathology</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychology. Psychophysiology</topic><topic>Psychopathology. Psychiatry</topic><topic>Psychoses</topic><topic>Reaction Time - drug effects</topic><topic>Reward</topic><topic>Schizophrenia</topic><topic>spatial working memory</topic><topic>Time Factors</topic><topic>Visual Perception - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Castner, Stacy A.</creatorcontrib><creatorcontrib>Vosler, Peter S.</creatorcontrib><creatorcontrib>Goldman-Rakic, Patricia S.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><jtitle>Biological psychiatry (1969)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Castner, Stacy A.</au><au>Vosler, Peter S.</au><au>Goldman-Rakic, Patricia S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Amphetamine sensitization impairs cognition and reduces dopamine turnover in primate prefrontal cortex</atitle><jtitle>Biological psychiatry (1969)</jtitle><addtitle>Biol Psychiatry</addtitle><date>2005-04-01</date><risdate>2005</risdate><volume>57</volume><issue>7</issue><spage>743</spage><epage>751</epage><pages>743-751</pages><issn>0006-3223</issn><eissn>1873-2402</eissn><coden>BIPCBF</coden><abstract>Amphetamine (AMPH) sensitization in monkeys produces long-lasting behavioral changes that model positive (hallucinatory-like behaviors) and negative (psychomotor depression) symptoms of schizophrenia. The extent to which this model produces the core deficit in schizophrenia—working memory impairment—is unknown.
Two groups of rhesus monkeys were sensitized to AMPH over 6 weeks. In one group, acquisition of cognitive tasks (delayed response, visual discrimination, delayed nonmatch-to-sample) was examined beginning 6+ months postsensitization. The second group was pretrained to stability on delayed response before sensitization. Regional postmortem concentrations of dopamine and its metabolites were examined in tissue from age-matched AMPH-naïve and AMPH-sensitized monkeys using high-performance liquid chromatography with electrochemical detection (HPLC-ECD).
The AMPH-sensitized monkeys were profoundly impaired in their ability to acquire cognitive tasks compared with AMPH-naïve monkeys. Pretrained monkeys showed impaired delayed response performance for several months following sensitization. Analysis by HPLC revealed that AMPH sensitization significantly reduced dopamine turnover in prefrontal cortex and striatum.
Impairments in the acquisition and performance of spatial delayed response in association with reduced dopamine turnover in prefrontal cortex following AMPH sensitization provide further support for the relevance of this model to both the etiology and the treatment of cognitive dysfunction in schizophrenia.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>15820231</pmid><doi>10.1016/j.biopsych.2004.12.019</doi><tpages>9</tpages></addata></record> |
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| ispartof | Biological psychiatry (1969), 2005-04, Vol.57 (7), p.743-751 |
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| subjects | 3,4-Dihydroxyphenylacetic Acid - metabolism Adult and adolescent clinical studies Amphetamine - adverse effects Amphetamine - pharmacology Analysis of Variance Animals Behavior, Animal - drug effects Behavioral psychophysiology Behavioral sensitization Biological and medical sciences Central Nervous System Stimulants - adverse effects Central Nervous System Stimulants - pharmacology Chromatography, High Pressure Liquid - methods Cognition Disorders - chemically induced Cognition Disorders - physiopathology Corpus Striatum - metabolism Discrimination Learning - drug effects Dopamine - metabolism dopamine transmission dorsolateral prefrontal cortex Electrochemistry - methods Female Fundamental and applied biological sciences. Psychology Homovanillic Acid - metabolism Macaca mulatta Male Medical sciences Neuropsychological Tests - statistics & numerical data Neurotransmission and behavior nonhuman primate Prefrontal Cortex - drug effects Prefrontal Cortex - metabolism Prefrontal Cortex - physiopathology Psychology. Psychoanalysis. Psychiatry Psychology. Psychophysiology Psychopathology. Psychiatry Psychoses Reaction Time - drug effects Reward Schizophrenia spatial working memory Time Factors Visual Perception - drug effects |
| title | Amphetamine sensitization impairs cognition and reduces dopamine turnover in primate prefrontal cortex |
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