Protective effects of the antioxidant sulforaphane on behavioral changes and neurotoxicity in mice after the administration of methamphetamine
Rationale Methamphetamine (METH) is a powerfully addictive stimulant associated with serious health conditions. Accumulating evidence suggests a role of oxidative stress in METH-induced behavioral abnormalities. Sulforaphane (SFN), found in cruciferous vegetables, is a potent antioxidant. It is of i...
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| Veröffentlicht in: | Psychopharmacologia 2012-07, Vol.222 (1), p.37-45 |
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| creator | Chen, Hongxian Wu, Jin Zhang, Jichun Fujita, Yuko Ishima, Tamaki Iyo, Masaomi Hashimoto, Kenji |
| description | Rationale
Methamphetamine (METH) is a powerfully addictive stimulant associated with serious health conditions. Accumulating evidence suggests a role of oxidative stress in METH-induced behavioral abnormalities. Sulforaphane (SFN), found in cruciferous vegetables, is a potent antioxidant. It is of interest to determine whether SFN can attenuate behavioral and neuropathological changes associated with METH exposure.
Objectives
This study was undertaken to examine the effects of SFN on behavioral changes and dopaminergic neurotoxicity in mice exposed to METH.
Methods
The effects of SFN on acute hyperlocomotion and the development of behavioral sensitization induced by the administration of METH were examined. Levels of dopamine (DA) and its major metabolite 3,4-dihydroxyphenyl acetic acid (DOPAC) in the striatum were measured. In addition, DA transporter (DAT) immunoreactivity was also performed.
Results
Pretreatment with SFN at 1, 3, and 10 mg/kg elicited a dose-dependent attenuation of acute hyperlocomotion in mice, after a single administration of METH (3 mg/kg). The development of behavioral sensitization after repeated administrations of METH (3 mg/kg/day, once daily for 5 days) was significantly reduced by pretreatment with SFN (10 mg/kg). In addition, the lowering of DA levels and DOPAC as well as DAT immunoreactivity in the striatum, usually seen after repeated administration of METH, was significantly attenuated by both pretreatment and the subsequent administration of SFN. Furthermore, SFN significantly reduced microglial activation in the striatum after repeated exposure to METH.
Conclusion
It is therefore likely that SFN can be a useful drug for the treatment of signs associated with METH abuse in humans. |
| doi_str_mv | 10.1007/s00213-011-2619-3 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_1028028160</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A354577847</galeid><sourcerecordid>A354577847</sourcerecordid><originalsourceid>FETCH-LOGICAL-c568t-642426bfc04d07465171507354fad9d084af7a02741e7441d96de63924a7e49a3</originalsourceid><addsrcrecordid>eNp1ks9u1DAQxiMEokvhAbggSwiJS8rYcezkWFX8kyrBAc6R1xl3XSX2YjtV-xI8M7PKQgFBEsnW-Pd9MxNPVT3ncMYB9JsMIHhTA-e1ULyvmwfVhstG1AK0eFhtAJqmbnjbnVRPcr4GemQnH1cnQgiArodN9f1zigVt8TfI0DnaZRYdKztkJhQfb_1IK8vL5GIy-50JyGJgW9yZG0-RiVmKXWEmfGQBF7IjkfXljvnAZm_JyBVMq-U4--BzSYaswyHRjGVn5v0Oi6EjfFo9cmbK-Oy4nlZf3739cvGhvvz0_uPF-WVtW9WVWkkhhdo6C3IELVXLNW9BN610ZuxH6KRx2oDQkqOWko-9GlE1vZBGo-xNc1q9Xn33KX5bMJdh9tniNFF_cckDB9HRxxUQ-vIv9DouKVB1RPFOiZ5LcU9dmQkHH1ykJu3BdDinslqtO6mJOvsHRe-I9KdiQOcp_oeArwKbYs4J3bBPfjbpjnIPhxkY1hkYaAaGwwwMDWleHAtetjOOvxQ_L52AV0fAZGsml0ywPt9zCkC1QhEnVi7TEd1x-r3z_2X_AYqYyJ4</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1018629142</pqid></control><display><type>article</type><title>Protective effects of the antioxidant sulforaphane on behavioral changes and neurotoxicity in mice after the administration of methamphetamine</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Chen, Hongxian ; Wu, Jin ; Zhang, Jichun ; Fujita, Yuko ; Ishima, Tamaki ; Iyo, Masaomi ; Hashimoto, Kenji</creator><creatorcontrib>Chen, Hongxian ; Wu, Jin ; Zhang, Jichun ; Fujita, Yuko ; Ishima, Tamaki ; Iyo, Masaomi ; Hashimoto, Kenji</creatorcontrib><description>Rationale
Methamphetamine (METH) is a powerfully addictive stimulant associated with serious health conditions. Accumulating evidence suggests a role of oxidative stress in METH-induced behavioral abnormalities. Sulforaphane (SFN), found in cruciferous vegetables, is a potent antioxidant. It is of interest to determine whether SFN can attenuate behavioral and neuropathological changes associated with METH exposure.
Objectives
This study was undertaken to examine the effects of SFN on behavioral changes and dopaminergic neurotoxicity in mice exposed to METH.
Methods
The effects of SFN on acute hyperlocomotion and the development of behavioral sensitization induced by the administration of METH were examined. Levels of dopamine (DA) and its major metabolite 3,4-dihydroxyphenyl acetic acid (DOPAC) in the striatum were measured. In addition, DA transporter (DAT) immunoreactivity was also performed.
Results
Pretreatment with SFN at 1, 3, and 10 mg/kg elicited a dose-dependent attenuation of acute hyperlocomotion in mice, after a single administration of METH (3 mg/kg). The development of behavioral sensitization after repeated administrations of METH (3 mg/kg/day, once daily for 5 days) was significantly reduced by pretreatment with SFN (10 mg/kg). In addition, the lowering of DA levels and DOPAC as well as DAT immunoreactivity in the striatum, usually seen after repeated administration of METH, was significantly attenuated by both pretreatment and the subsequent administration of SFN. Furthermore, SFN significantly reduced microglial activation in the striatum after repeated exposure to METH.
Conclusion
It is therefore likely that SFN can be a useful drug for the treatment of signs associated with METH abuse in humans.</description><identifier>ISSN: 0033-3158</identifier><identifier>EISSN: 1432-2072</identifier><identifier>DOI: 10.1007/s00213-011-2619-3</identifier><identifier>PMID: 22200890</identifier><identifier>CODEN: PSYPAG</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>3,4-Dihydroxyphenylacetic Acid - metabolism ; Acetic acid ; Animals ; Antioxidants ; Antioxidants - administration & dosage ; Antioxidants - pharmacology ; Basal Ganglia - drug effects ; Basal Ganglia - metabolism ; Behavior modification ; Behavior, Animal - drug effects ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Dopamine - metabolism ; Dopamine transporter ; Dosage and administration ; Dose-Response Relationship, Drug ; Drug abuse ; Immunoreactivity ; Isothiocyanates ; Male ; Medical sciences ; Metabolites ; Methamphetamine ; Methamphetamine - administration & dosage ; Methamphetamine - toxicity ; Mice ; Mice, Inbred BALB C ; Microglia - drug effects ; Microglia - metabolism ; Motor Activity - drug effects ; Neostriatum ; Neuropharmacology ; Neuroprotective Agents - administration & dosage ; Neuroprotective Agents - pharmacology ; Neurosciences ; Neurotoxicity ; Neurotoxicity Syndromes - etiology ; Neurotoxicity Syndromes - prevention & control ; Organic acids ; Original Investigation ; Oxidative stress ; Pharmacology. Drug treatments ; Pharmacology/Toxicology ; Psychiatry ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) ; Psychology. Psychoanalysis. Psychiatry ; Psychopharmacology ; Stimulants ; Sulforafan ; Thiocyanates - administration & dosage ; Thiocyanates - pharmacology ; Vegetables</subject><ispartof>Psychopharmacologia, 2012-07, Vol.222 (1), p.37-45</ispartof><rights>Springer-Verlag 2011</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2012 Springer</rights><rights>Springer-Verlag 2012</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c568t-642426bfc04d07465171507354fad9d084af7a02741e7441d96de63924a7e49a3</citedby><cites>FETCH-LOGICAL-c568t-642426bfc04d07465171507354fad9d084af7a02741e7441d96de63924a7e49a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00213-011-2619-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00213-011-2619-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26006526$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22200890$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Hongxian</creatorcontrib><creatorcontrib>Wu, Jin</creatorcontrib><creatorcontrib>Zhang, Jichun</creatorcontrib><creatorcontrib>Fujita, Yuko</creatorcontrib><creatorcontrib>Ishima, Tamaki</creatorcontrib><creatorcontrib>Iyo, Masaomi</creatorcontrib><creatorcontrib>Hashimoto, Kenji</creatorcontrib><title>Protective effects of the antioxidant sulforaphane on behavioral changes and neurotoxicity in mice after the administration of methamphetamine</title><title>Psychopharmacologia</title><addtitle>Psychopharmacology</addtitle><addtitle>Psychopharmacology (Berl)</addtitle><description>Rationale
Methamphetamine (METH) is a powerfully addictive stimulant associated with serious health conditions. Accumulating evidence suggests a role of oxidative stress in METH-induced behavioral abnormalities. Sulforaphane (SFN), found in cruciferous vegetables, is a potent antioxidant. It is of interest to determine whether SFN can attenuate behavioral and neuropathological changes associated with METH exposure.
Objectives
This study was undertaken to examine the effects of SFN on behavioral changes and dopaminergic neurotoxicity in mice exposed to METH.
Methods
The effects of SFN on acute hyperlocomotion and the development of behavioral sensitization induced by the administration of METH were examined. Levels of dopamine (DA) and its major metabolite 3,4-dihydroxyphenyl acetic acid (DOPAC) in the striatum were measured. In addition, DA transporter (DAT) immunoreactivity was also performed.
Results
Pretreatment with SFN at 1, 3, and 10 mg/kg elicited a dose-dependent attenuation of acute hyperlocomotion in mice, after a single administration of METH (3 mg/kg). The development of behavioral sensitization after repeated administrations of METH (3 mg/kg/day, once daily for 5 days) was significantly reduced by pretreatment with SFN (10 mg/kg). In addition, the lowering of DA levels and DOPAC as well as DAT immunoreactivity in the striatum, usually seen after repeated administration of METH, was significantly attenuated by both pretreatment and the subsequent administration of SFN. Furthermore, SFN significantly reduced microglial activation in the striatum after repeated exposure to METH.
Conclusion
It is therefore likely that SFN can be a useful drug for the treatment of signs associated with METH abuse in humans.</description><subject>3,4-Dihydroxyphenylacetic Acid - metabolism</subject><subject>Acetic acid</subject><subject>Animals</subject><subject>Antioxidants</subject><subject>Antioxidants - administration & dosage</subject><subject>Antioxidants - pharmacology</subject><subject>Basal Ganglia - drug effects</subject><subject>Basal Ganglia - metabolism</subject><subject>Behavior modification</subject><subject>Behavior, Animal - drug effects</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Dopamine - metabolism</subject><subject>Dopamine transporter</subject><subject>Dosage and administration</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug abuse</subject><subject>Immunoreactivity</subject><subject>Isothiocyanates</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metabolites</subject><subject>Methamphetamine</subject><subject>Methamphetamine - administration & dosage</subject><subject>Methamphetamine - toxicity</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Microglia - drug effects</subject><subject>Microglia - metabolism</subject><subject>Motor Activity - drug effects</subject><subject>Neostriatum</subject><subject>Neuropharmacology</subject><subject>Neuroprotective Agents - administration & dosage</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Neurosciences</subject><subject>Neurotoxicity</subject><subject>Neurotoxicity Syndromes - etiology</subject><subject>Neurotoxicity Syndromes - prevention & control</subject><subject>Organic acids</subject><subject>Original Investigation</subject><subject>Oxidative stress</subject><subject>Pharmacology. Drug treatments</subject><subject>Pharmacology/Toxicology</subject><subject>Psychiatry</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>Psychopharmacology</subject><subject>Stimulants</subject><subject>Sulforafan</subject><subject>Thiocyanates - administration & dosage</subject><subject>Thiocyanates - pharmacology</subject><subject>Vegetables</subject><issn>0033-3158</issn><issn>1432-2072</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</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>eNp1ks9u1DAQxiMEokvhAbggSwiJS8rYcezkWFX8kyrBAc6R1xl3XSX2YjtV-xI8M7PKQgFBEsnW-Pd9MxNPVT3ncMYB9JsMIHhTA-e1ULyvmwfVhstG1AK0eFhtAJqmbnjbnVRPcr4GemQnH1cnQgiArodN9f1zigVt8TfI0DnaZRYdKztkJhQfb_1IK8vL5GIy-50JyGJgW9yZG0-RiVmKXWEmfGQBF7IjkfXljvnAZm_JyBVMq-U4--BzSYaswyHRjGVn5v0Oi6EjfFo9cmbK-Oy4nlZf3739cvGhvvz0_uPF-WVtW9WVWkkhhdo6C3IELVXLNW9BN610ZuxH6KRx2oDQkqOWko-9GlE1vZBGo-xNc1q9Xn33KX5bMJdh9tniNFF_cckDB9HRxxUQ-vIv9DouKVB1RPFOiZ5LcU9dmQkHH1ykJu3BdDinslqtO6mJOvsHRe-I9KdiQOcp_oeArwKbYs4J3bBPfjbpjnIPhxkY1hkYaAaGwwwMDWleHAtetjOOvxQ_L52AV0fAZGsml0ywPt9zCkC1QhEnVi7TEd1x-r3z_2X_AYqYyJ4</recordid><startdate>20120701</startdate><enddate>20120701</enddate><creator>Chen, Hongxian</creator><creator>Wu, Jin</creator><creator>Zhang, Jichun</creator><creator>Fujita, Yuko</creator><creator>Ishima, Tamaki</creator><creator>Iyo, Masaomi</creator><creator>Hashimoto, Kenji</creator><general>Springer-Verlag</general><general>Springer</general><general>Springer Nature B.V</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>3V.</scope><scope>7QG</scope><scope>7QR</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FD</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>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope></search><sort><creationdate>20120701</creationdate><title>Protective effects of the antioxidant sulforaphane on behavioral changes and neurotoxicity in mice after the administration of methamphetamine</title><author>Chen, Hongxian ; Wu, Jin ; Zhang, Jichun ; Fujita, Yuko ; Ishima, Tamaki ; Iyo, Masaomi ; Hashimoto, Kenji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c568t-642426bfc04d07465171507354fad9d084af7a02741e7441d96de63924a7e49a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>3,4-Dihydroxyphenylacetic Acid - metabolism</topic><topic>Acetic acid</topic><topic>Animals</topic><topic>Antioxidants</topic><topic>Antioxidants - administration & dosage</topic><topic>Antioxidants - pharmacology</topic><topic>Basal Ganglia - drug effects</topic><topic>Basal Ganglia - metabolism</topic><topic>Behavior modification</topic><topic>Behavior, Animal - drug effects</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Dopamine - metabolism</topic><topic>Dopamine transporter</topic><topic>Dosage and administration</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug abuse</topic><topic>Immunoreactivity</topic><topic>Isothiocyanates</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metabolites</topic><topic>Methamphetamine</topic><topic>Methamphetamine - administration & dosage</topic><topic>Methamphetamine - toxicity</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Microglia - drug effects</topic><topic>Microglia - metabolism</topic><topic>Motor Activity - drug effects</topic><topic>Neostriatum</topic><topic>Neuropharmacology</topic><topic>Neuroprotective Agents - administration & dosage</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Neurosciences</topic><topic>Neurotoxicity</topic><topic>Neurotoxicity Syndromes - etiology</topic><topic>Neurotoxicity Syndromes - prevention & control</topic><topic>Organic acids</topic><topic>Original Investigation</topic><topic>Oxidative stress</topic><topic>Pharmacology. Drug treatments</topic><topic>Pharmacology/Toxicology</topic><topic>Psychiatry</topic><topic>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer</topic><topic>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopharmacology</topic><topic>Stimulants</topic><topic>Sulforafan</topic><topic>Thiocyanates - administration & dosage</topic><topic>Thiocyanates - pharmacology</topic><topic>Vegetables</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Hongxian</creatorcontrib><creatorcontrib>Wu, Jin</creatorcontrib><creatorcontrib>Zhang, Jichun</creatorcontrib><creatorcontrib>Fujita, Yuko</creatorcontrib><creatorcontrib>Ishima, Tamaki</creatorcontrib><creatorcontrib>Iyo, Masaomi</creatorcontrib><creatorcontrib>Hashimoto, Kenji</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>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & 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>Technology Research Database</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>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</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><jtitle>Psychopharmacologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Hongxian</au><au>Wu, Jin</au><au>Zhang, Jichun</au><au>Fujita, Yuko</au><au>Ishima, Tamaki</au><au>Iyo, Masaomi</au><au>Hashimoto, Kenji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protective effects of the antioxidant sulforaphane on behavioral changes and neurotoxicity in mice after the administration of methamphetamine</atitle><jtitle>Psychopharmacologia</jtitle><stitle>Psychopharmacology</stitle><addtitle>Psychopharmacology (Berl)</addtitle><date>2012-07-01</date><risdate>2012</risdate><volume>222</volume><issue>1</issue><spage>37</spage><epage>45</epage><pages>37-45</pages><issn>0033-3158</issn><eissn>1432-2072</eissn><coden>PSYPAG</coden><abstract>Rationale
Methamphetamine (METH) is a powerfully addictive stimulant associated with serious health conditions. Accumulating evidence suggests a role of oxidative stress in METH-induced behavioral abnormalities. Sulforaphane (SFN), found in cruciferous vegetables, is a potent antioxidant. It is of interest to determine whether SFN can attenuate behavioral and neuropathological changes associated with METH exposure.
Objectives
This study was undertaken to examine the effects of SFN on behavioral changes and dopaminergic neurotoxicity in mice exposed to METH.
Methods
The effects of SFN on acute hyperlocomotion and the development of behavioral sensitization induced by the administration of METH were examined. Levels of dopamine (DA) and its major metabolite 3,4-dihydroxyphenyl acetic acid (DOPAC) in the striatum were measured. In addition, DA transporter (DAT) immunoreactivity was also performed.
Results
Pretreatment with SFN at 1, 3, and 10 mg/kg elicited a dose-dependent attenuation of acute hyperlocomotion in mice, after a single administration of METH (3 mg/kg). The development of behavioral sensitization after repeated administrations of METH (3 mg/kg/day, once daily for 5 days) was significantly reduced by pretreatment with SFN (10 mg/kg). In addition, the lowering of DA levels and DOPAC as well as DAT immunoreactivity in the striatum, usually seen after repeated administration of METH, was significantly attenuated by both pretreatment and the subsequent administration of SFN. Furthermore, SFN significantly reduced microglial activation in the striatum after repeated exposure to METH.
Conclusion
It is therefore likely that SFN can be a useful drug for the treatment of signs associated with METH abuse in humans.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>22200890</pmid><doi>10.1007/s00213-011-2619-3</doi><tpages>9</tpages></addata></record> |
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| subjects | 3,4-Dihydroxyphenylacetic Acid - metabolism Acetic acid Animals Antioxidants Antioxidants - administration & dosage Antioxidants - pharmacology Basal Ganglia - drug effects Basal Ganglia - metabolism Behavior modification Behavior, Animal - drug effects Biological and medical sciences Biomedical and Life Sciences Biomedicine Dopamine - metabolism Dopamine transporter Dosage and administration Dose-Response Relationship, Drug Drug abuse Immunoreactivity Isothiocyanates Male Medical sciences Metabolites Methamphetamine Methamphetamine - administration & dosage Methamphetamine - toxicity Mice Mice, Inbred BALB C Microglia - drug effects Microglia - metabolism Motor Activity - drug effects Neostriatum Neuropharmacology Neuroprotective Agents - administration & dosage Neuroprotective Agents - pharmacology Neurosciences Neurotoxicity Neurotoxicity Syndromes - etiology Neurotoxicity Syndromes - prevention & control Organic acids Original Investigation Oxidative stress Pharmacology. Drug treatments Pharmacology/Toxicology Psychiatry Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) Psychology. Psychoanalysis. Psychiatry Psychopharmacology Stimulants Sulforafan Thiocyanates - administration & dosage Thiocyanates - pharmacology Vegetables |
| title | Protective effects of the antioxidant sulforaphane on behavioral changes and neurotoxicity in mice after the administration of methamphetamine |
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