Interaction of glutathione depletion and psychotropic drug treatment in prepulse inhibition in rats and mice
Oxidative stress has been implicated in several psychiatric illnesses, including schizophrenia. Glutathione is the brain's primary antioxidant and decreased levels of brain glutathione are reported in schizophrenia. Prepulse inhibition (PPI) is a measure of sensory gating, and PPI is reduced in...
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| Veröffentlicht in: | Pharmacology, biochemistry and behavior biochemistry and behavior, 2010-12, Vol.97 (2), p.293-300 |
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| creator | Dean, Olivia Bush, Ashley I. Berk, Michael Copolov, David L. van den Buuse, Maarten |
| description | Oxidative stress has been implicated in several psychiatric illnesses, including schizophrenia. Glutathione is the brain's primary antioxidant and decreased levels of brain glutathione are reported in schizophrenia. Prepulse inhibition (PPI) is a measure of sensory gating, and PPI is reduced in schizophrenia. This study aimed to investigate the effects of brain glutathione depletion on PPI regulation.
Rats and mice were treated with the glutathione-depleting agent, 2-cyclohexene-1-one (CHX), and tested for baseline PPI and its disruption by treatment with amphetamine and MK-801.
Treatment with CHX caused significant depletion of GSH in frontal cortex and striatum of rats and mice. Baseline PPI and startle were not altered. However, the disruption of PPI after treatment with amphetamine was absent in CHX-treated rats. In contrast, the effect of MK-801 was not altered by CHX-treatment, nor was there any effect of CHX treatment in mice.
These data show an interaction of glutathione depletion with the effects of amphetamine treatment on PPI in rats. This effect could reflect loss of plasticity in PPI regulation caused by the additive effects of CHX-induced glutathione depletion and additional oxidative stress caused by amphetamine-induced dopamine release. The significance of these results for schizophrenia is discussed.
►
Brain glutathione depletion (BGD) did not disrupt baseline prepulse inhibition (PPI) in rats or mice.
►
After BGD, amphetamine treatment failed to reduce PPI in rats.
►
BGD did not alter the effect of MK-801 treatment on PPI in rats.
►
BGD did not alter the effect of either amphetamine or MK-801 in mice.
►
BGD may impair dopaminergic modulation of PPI in rats. |
| doi_str_mv | 10.1016/j.pbb.2010.08.013 |
| format | Article |
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Rats and mice were treated with the glutathione-depleting agent, 2-cyclohexene-1-one (CHX), and tested for baseline PPI and its disruption by treatment with amphetamine and MK-801.
Treatment with CHX caused significant depletion of GSH in frontal cortex and striatum of rats and mice. Baseline PPI and startle were not altered. However, the disruption of PPI after treatment with amphetamine was absent in CHX-treated rats. In contrast, the effect of MK-801 was not altered by CHX-treatment, nor was there any effect of CHX treatment in mice.
These data show an interaction of glutathione depletion with the effects of amphetamine treatment on PPI in rats. This effect could reflect loss of plasticity in PPI regulation caused by the additive effects of CHX-induced glutathione depletion and additional oxidative stress caused by amphetamine-induced dopamine release. The significance of these results for schizophrenia is discussed.
►
Brain glutathione depletion (BGD) did not disrupt baseline prepulse inhibition (PPI) in rats or mice.
►
After BGD, amphetamine treatment failed to reduce PPI in rats.
►
BGD did not alter the effect of MK-801 treatment on PPI in rats.
►
BGD did not alter the effect of either amphetamine or MK-801 in mice.
►
BGD may impair dopaminergic modulation of PPI in rats.</description><identifier>ISSN: 0091-3057</identifier><identifier>EISSN: 1873-5177</identifier><identifier>DOI: 10.1016/j.pbb.2010.08.013</identifier><identifier>PMID: 20816888</identifier><identifier>CODEN: PBBHAU</identifier><language>eng</language><publisher>Kidlington: Elsevier Inc</publisher><subject>Acoustic Stimulation ; Adult and adolescent clinical studies ; Amphetamine ; Amphetamine - pharmacology ; Animals ; Biological and medical sciences ; Brain Chemistry - drug effects ; Cyclohexanones - pharmacology ; Dizocilpine Maleate - pharmacology ; Dopamine Agents - pharmacology ; Excitatory Amino Acid Antagonists - pharmacology ; Glutathione ; Glutathione - metabolism ; Glutathione - physiology ; Habituation, Psychophysiologic - drug effects ; Male ; Medical sciences ; Mice ; Mice, Inbred C57BL ; MK-801 ; Neuropharmacology ; Pharmacology. Drug treatments ; Prepulse inhibition ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Psychopharmacology ; Psychoses ; Psychotropic Drugs - pharmacology ; Rats ; Rats, Sprague-Dawley ; Reflex, Startle - drug effects ; Schizophrenia ; Sensory Gating ; Startle</subject><ispartof>Pharmacology, biochemistry and behavior, 2010-12, Vol.97 (2), p.293-300</ispartof><rights>2010 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2010 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c414t-7b60f5bf0e7b152a6070370e5a29103eb825a679b92319f96ddf75c96c907b983</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0091305710002583$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23395180$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20816888$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dean, Olivia</creatorcontrib><creatorcontrib>Bush, Ashley I.</creatorcontrib><creatorcontrib>Berk, Michael</creatorcontrib><creatorcontrib>Copolov, David L.</creatorcontrib><creatorcontrib>van den Buuse, Maarten</creatorcontrib><title>Interaction of glutathione depletion and psychotropic drug treatment in prepulse inhibition in rats and mice</title><title>Pharmacology, biochemistry and behavior</title><addtitle>Pharmacol Biochem Behav</addtitle><description>Oxidative stress has been implicated in several psychiatric illnesses, including schizophrenia. Glutathione is the brain's primary antioxidant and decreased levels of brain glutathione are reported in schizophrenia. Prepulse inhibition (PPI) is a measure of sensory gating, and PPI is reduced in schizophrenia. This study aimed to investigate the effects of brain glutathione depletion on PPI regulation.
Rats and mice were treated with the glutathione-depleting agent, 2-cyclohexene-1-one (CHX), and tested for baseline PPI and its disruption by treatment with amphetamine and MK-801.
Treatment with CHX caused significant depletion of GSH in frontal cortex and striatum of rats and mice. Baseline PPI and startle were not altered. However, the disruption of PPI after treatment with amphetamine was absent in CHX-treated rats. In contrast, the effect of MK-801 was not altered by CHX-treatment, nor was there any effect of CHX treatment in mice.
These data show an interaction of glutathione depletion with the effects of amphetamine treatment on PPI in rats. This effect could reflect loss of plasticity in PPI regulation caused by the additive effects of CHX-induced glutathione depletion and additional oxidative stress caused by amphetamine-induced dopamine release. The significance of these results for schizophrenia is discussed.
►
Brain glutathione depletion (BGD) did not disrupt baseline prepulse inhibition (PPI) in rats or mice.
►
After BGD, amphetamine treatment failed to reduce PPI in rats.
►
BGD did not alter the effect of MK-801 treatment on PPI in rats.
►
BGD did not alter the effect of either amphetamine or MK-801 in mice.
►
BGD may impair dopaminergic modulation of PPI in rats.</description><subject>Acoustic Stimulation</subject><subject>Adult and adolescent clinical studies</subject><subject>Amphetamine</subject><subject>Amphetamine - pharmacology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Brain Chemistry - drug effects</subject><subject>Cyclohexanones - pharmacology</subject><subject>Dizocilpine Maleate - pharmacology</subject><subject>Dopamine Agents - pharmacology</subject><subject>Excitatory Amino Acid Antagonists - pharmacology</subject><subject>Glutathione</subject><subject>Glutathione - metabolism</subject><subject>Glutathione - physiology</subject><subject>Habituation, Psychophysiologic - drug effects</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>MK-801</subject><subject>Neuropharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Prepulse inhibition</subject><subject>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer</subject><subject>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Psychopharmacology</subject><subject>Psychoses</subject><subject>Psychotropic Drugs - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reflex, Startle - drug effects</subject><subject>Schizophrenia</subject><subject>Sensory Gating</subject><subject>Startle</subject><issn>0091-3057</issn><issn>1873-5177</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtP3TAQha2qqNzS_oBuqmyqrnIZx3Fsi1WFSouExAbWlu1MuL7KC9upxL_H9wHsympm7O8cjeYQ8o3CmgJtzrfr2dp1BXkGuQbKPpAVlYKVnArxkawAFC0ZcHFKPse4BYC6asQnclqBpI2UckX66zFhMC75aSymrnjol2TSJk9YtDj3uP8wY1vM8cltphSm2buiDctDkQKaNOCYCj8Wc8B56SPmfuOt38vyczAp7uWDd_iFnHQmM1-P9YzcX_2-u_xb3tz-ub78dVO6mtapFLaBjtsOUFjKK9OAACYAuakUBYZWVtw0QllVMao61bRtJ7hTjVMgrJLsjPw8-M5helwwJj346LDvzYjTErUEkZ1qRd8lBc8QrWHnSQ-kC1OMATs9Bz-Y8KQp6F0aeqtzGnqXhgapcxpZ8_3ovtgB21fFy_kz8OMImOhM3wUzOh_fOMYUpxIyd3HgMF_tn8ego_M4Omx9QJd0O_n_rPEMNKun-Q</recordid><startdate>20101201</startdate><enddate>20101201</enddate><creator>Dean, Olivia</creator><creator>Bush, Ashley I.</creator><creator>Berk, Michael</creator><creator>Copolov, David L.</creator><creator>van den Buuse, Maarten</creator><general>Elsevier Inc</general><general>Elsevier</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>7X8</scope><scope>7QG</scope><scope>7TK</scope></search><sort><creationdate>20101201</creationdate><title>Interaction of glutathione depletion and psychotropic drug treatment in prepulse inhibition in rats and mice</title><author>Dean, Olivia ; Bush, Ashley I. ; Berk, Michael ; Copolov, David L. ; van den Buuse, Maarten</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c414t-7b60f5bf0e7b152a6070370e5a29103eb825a679b92319f96ddf75c96c907b983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Acoustic Stimulation</topic><topic>Adult and adolescent clinical studies</topic><topic>Amphetamine</topic><topic>Amphetamine - pharmacology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Brain Chemistry - drug effects</topic><topic>Cyclohexanones - pharmacology</topic><topic>Dizocilpine Maleate - pharmacology</topic><topic>Dopamine Agents - pharmacology</topic><topic>Excitatory Amino Acid Antagonists - pharmacology</topic><topic>Glutathione</topic><topic>Glutathione - metabolism</topic><topic>Glutathione - physiology</topic><topic>Habituation, Psychophysiologic - drug effects</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>MK-801</topic><topic>Neuropharmacology</topic><topic>Pharmacology. 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Psychiatry</topic><topic>Psychopharmacology</topic><topic>Psychoses</topic><topic>Psychotropic Drugs - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Reflex, Startle - drug effects</topic><topic>Schizophrenia</topic><topic>Sensory Gating</topic><topic>Startle</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dean, Olivia</creatorcontrib><creatorcontrib>Bush, Ashley I.</creatorcontrib><creatorcontrib>Berk, Michael</creatorcontrib><creatorcontrib>Copolov, David L.</creatorcontrib><creatorcontrib>van den Buuse, Maarten</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>MEDLINE - Academic</collection><collection>Animal Behavior Abstracts</collection><collection>Neurosciences Abstracts</collection><jtitle>Pharmacology, biochemistry and behavior</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dean, Olivia</au><au>Bush, Ashley I.</au><au>Berk, Michael</au><au>Copolov, David L.</au><au>van den Buuse, Maarten</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interaction of glutathione depletion and psychotropic drug treatment in prepulse inhibition in rats and mice</atitle><jtitle>Pharmacology, biochemistry and behavior</jtitle><addtitle>Pharmacol Biochem Behav</addtitle><date>2010-12-01</date><risdate>2010</risdate><volume>97</volume><issue>2</issue><spage>293</spage><epage>300</epage><pages>293-300</pages><issn>0091-3057</issn><eissn>1873-5177</eissn><coden>PBBHAU</coden><abstract>Oxidative stress has been implicated in several psychiatric illnesses, including schizophrenia. Glutathione is the brain's primary antioxidant and decreased levels of brain glutathione are reported in schizophrenia. Prepulse inhibition (PPI) is a measure of sensory gating, and PPI is reduced in schizophrenia. This study aimed to investigate the effects of brain glutathione depletion on PPI regulation.
Rats and mice were treated with the glutathione-depleting agent, 2-cyclohexene-1-one (CHX), and tested for baseline PPI and its disruption by treatment with amphetamine and MK-801.
Treatment with CHX caused significant depletion of GSH in frontal cortex and striatum of rats and mice. Baseline PPI and startle were not altered. However, the disruption of PPI after treatment with amphetamine was absent in CHX-treated rats. In contrast, the effect of MK-801 was not altered by CHX-treatment, nor was there any effect of CHX treatment in mice.
These data show an interaction of glutathione depletion with the effects of amphetamine treatment on PPI in rats. This effect could reflect loss of plasticity in PPI regulation caused by the additive effects of CHX-induced glutathione depletion and additional oxidative stress caused by amphetamine-induced dopamine release. The significance of these results for schizophrenia is discussed.
►
Brain glutathione depletion (BGD) did not disrupt baseline prepulse inhibition (PPI) in rats or mice.
►
After BGD, amphetamine treatment failed to reduce PPI in rats.
►
BGD did not alter the effect of MK-801 treatment on PPI in rats.
►
BGD did not alter the effect of either amphetamine or MK-801 in mice.
►
BGD may impair dopaminergic modulation of PPI in rats.</abstract><cop>Kidlington</cop><pub>Elsevier Inc</pub><pmid>20816888</pmid><doi>10.1016/j.pbb.2010.08.013</doi><tpages>8</tpages></addata></record> |
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| subjects | Acoustic Stimulation Adult and adolescent clinical studies Amphetamine Amphetamine - pharmacology Animals Biological and medical sciences Brain Chemistry - drug effects Cyclohexanones - pharmacology Dizocilpine Maleate - pharmacology Dopamine Agents - pharmacology Excitatory Amino Acid Antagonists - pharmacology Glutathione Glutathione - metabolism Glutathione - physiology Habituation, Psychophysiologic - drug effects Male Medical sciences Mice Mice, Inbred C57BL MK-801 Neuropharmacology Pharmacology. Drug treatments Prepulse inhibition Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychopharmacology Psychoses Psychotropic Drugs - pharmacology Rats Rats, Sprague-Dawley Reflex, Startle - drug effects Schizophrenia Sensory Gating Startle |
| title | Interaction of glutathione depletion and psychotropic drug treatment in prepulse inhibition in rats and mice |
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