7-Nitroindazole Attenuates 6-Hydroxydopamine-Induced Spatial Learning Deficits and Dopamine Neuron Loss in a Presymptomatic Animal Model of Parkinson's Disease
Parkinson's disease (PD) is a neurodegenerative disorder in which loss of dopaminergic (DA) neurons (>50%) in the substantia nigra (SN) precede most of the overt motor symptoms, making early diagnosis and treatment interventions difficult. Because PD has been associated with free radicals ge...
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| Veröffentlicht in: | Experimental and clinical psychopharmacology 2008-04, Vol.16 (2), p.178-189 |
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| creator | Haik, Kristi L Shear, Deborah A Hargrove, Chad Patton, Jared Mazei-Robison, Michelle Sandstrom, Michael I Dunbar, Gary L |
| description | Parkinson's disease (PD) is a neurodegenerative disorder in which loss of dopaminergic (DA) neurons (>50%) in the substantia nigra (SN) precede most of the overt motor symptoms, making early diagnosis and treatment interventions difficult. Because PD has been associated with free radicals generated by nitric oxide, this study tested whether treatments of 7-nitroindazole (7NI), a nitric-oxide-synthase inhibitor, could reduce cognitive deficits that often emerge before overt motor symptoms in a presymptomatic rat model of PD. Rats were given intraperitoneal injections of 50 mg/kg 7NI (or vehicle) just before receiving bilateral, intrastriatal injections of the DA-toxin, 6-hydroxydopamine (6-OHDA). The rats were then given a battery of motor tasks, and their learning ability was assessed using a spatial reversal task in a water-
T
maze. Results indicate that 7NI treatments attenuate 6-OHDA-induced spatial learning deficits and protect against DA cell loss in the SN, suggesting that 7NI may have potential as an early, presymptomatic pharmacotherapy for PD. |
| doi_str_mv | 10.1037/1064-1297.16.2.178 |
| format | Article |
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T
maze. Results indicate that 7NI treatments attenuate 6-OHDA-induced spatial learning deficits and protect against DA cell loss in the SN, suggesting that 7NI may have potential as an early, presymptomatic pharmacotherapy for PD.</description><identifier>ISSN: 1064-1297</identifier><identifier>EISSN: 1936-2293</identifier><identifier>DOI: 10.1037/1064-1297.16.2.178</identifier><identifier>PMID: 18489022</identifier><language>eng</language><publisher>United States: American Psychological Association</publisher><subject>Analysis of Variance ; Animal ; Animal Models ; Animals ; Behavior, Animal - drug effects ; Disease Models, Animal ; Dopamine ; Dopamine - metabolism ; Indazoles - therapeutic use ; Learning Disorders - chemically induced ; Learning Disorders - drug therapy ; Learning Disorders - pathology ; Male ; Maze Learning - drug effects ; NADP - metabolism ; Neurons - drug effects ; Neurons - metabolism ; Neuroprotective Agents - therapeutic use ; Oxidopamine ; Parkinson Disease - drug therapy ; Parkinson's Disease ; Psychomotor Performance - drug effects ; Rats ; Rats, Sprague-Dawley ; Spatial Behavior - drug effects ; Spatial Behavior - physiology ; Spatial Learning ; Substantia Nigra - pathology</subject><ispartof>Experimental and clinical psychopharmacology, 2008-04, Vol.16 (2), p.178-189</ispartof><rights>2008 American Psychological Association</rights><rights>2008, American Psychological Association</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a393t-63bb96880a459e38df2e0267b25b316b96a700e30dde39f4806175e0309b33f63</citedby><orcidid>0000-0002-2372-1420</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27915,27916</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18489022$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Mello, Nancy K</contributor><creatorcontrib>Haik, Kristi L</creatorcontrib><creatorcontrib>Shear, Deborah A</creatorcontrib><creatorcontrib>Hargrove, Chad</creatorcontrib><creatorcontrib>Patton, Jared</creatorcontrib><creatorcontrib>Mazei-Robison, Michelle</creatorcontrib><creatorcontrib>Sandstrom, Michael I</creatorcontrib><creatorcontrib>Dunbar, Gary L</creatorcontrib><title>7-Nitroindazole Attenuates 6-Hydroxydopamine-Induced Spatial Learning Deficits and Dopamine Neuron Loss in a Presymptomatic Animal Model of Parkinson's Disease</title><title>Experimental and clinical psychopharmacology</title><addtitle>Exp Clin Psychopharmacol</addtitle><description>Parkinson's disease (PD) is a neurodegenerative disorder in which loss of dopaminergic (DA) neurons (>50%) in the substantia nigra (SN) precede most of the overt motor symptoms, making early diagnosis and treatment interventions difficult. Because PD has been associated with free radicals generated by nitric oxide, this study tested whether treatments of 7-nitroindazole (7NI), a nitric-oxide-synthase inhibitor, could reduce cognitive deficits that often emerge before overt motor symptoms in a presymptomatic rat model of PD. Rats were given intraperitoneal injections of 50 mg/kg 7NI (or vehicle) just before receiving bilateral, intrastriatal injections of the DA-toxin, 6-hydroxydopamine (6-OHDA). The rats were then given a battery of motor tasks, and their learning ability was assessed using a spatial reversal task in a water-
T
maze. Results indicate that 7NI treatments attenuate 6-OHDA-induced spatial learning deficits and protect against DA cell loss in the SN, suggesting that 7NI may have potential as an early, presymptomatic pharmacotherapy for PD.</description><subject>Analysis of Variance</subject><subject>Animal</subject><subject>Animal Models</subject><subject>Animals</subject><subject>Behavior, Animal - drug effects</subject><subject>Disease Models, Animal</subject><subject>Dopamine</subject><subject>Dopamine - metabolism</subject><subject>Indazoles - therapeutic use</subject><subject>Learning Disorders - chemically induced</subject><subject>Learning Disorders - drug therapy</subject><subject>Learning Disorders - pathology</subject><subject>Male</subject><subject>Maze Learning - drug effects</subject><subject>NADP - metabolism</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Neuroprotective Agents - therapeutic use</subject><subject>Oxidopamine</subject><subject>Parkinson Disease - drug therapy</subject><subject>Parkinson's Disease</subject><subject>Psychomotor Performance - drug effects</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Spatial Behavior - drug effects</subject><subject>Spatial Behavior - physiology</subject><subject>Spatial Learning</subject><subject>Substantia Nigra - pathology</subject><issn>1064-1297</issn><issn>1936-2293</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkV9rFDEUxYMotq5-AR8kSMEHmW3-zGYmj0u32sL2D6jPITO5o2lnkmmSAccv41dtll3Rgk-5kN85l3sOQm8pWVLCq1NKRFlQJqslFUu2pFX9DB1TyUXBmOTP8_wHOEKvYrwjhJZcspfoiNZlLQljx-h3VVzbFLx1Rv_yPeB1SuAmnSBiUVzMJvifs_GjHqyD4tKZqQWDv4w6Wd3jLejgrPuON9DZ1qaItTN4c8DxNUzBO7z1MWLrsMa3AeI8jMkPWd_itbNDdrnyBnrsO3yrw7110bsPEW9sBB3hNXrR6T7Cm8O7QN8-nX89uyi2N58vz9bbQnPJUyF400hR10SXKwm8Nh0DwkTVsFXDqch_uiIEODEGuOzKmgharYBwIhvOO8EX6P3edwz-YYKY1J2fgssrlaBl5nmOfIHYHmpDPilAp8aQLwizokTtKlG7xNUucUWFYipXkkXvDs5TM4D5Kzl0kIGPe0CPWo1xbnXI4fQQ2ykEcEmNP_S_dif_p59ij7orpBI</recordid><startdate>200804</startdate><enddate>200804</enddate><creator>Haik, Kristi L</creator><creator>Shear, Deborah A</creator><creator>Hargrove, Chad</creator><creator>Patton, Jared</creator><creator>Mazei-Robison, Michelle</creator><creator>Sandstrom, Michael I</creator><creator>Dunbar, Gary L</creator><general>American Psychological Association</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>7RZ</scope><scope>PSYQQ</scope><orcidid>https://orcid.org/0000-0002-2372-1420</orcidid></search><sort><creationdate>200804</creationdate><title>7-Nitroindazole Attenuates 6-Hydroxydopamine-Induced Spatial Learning Deficits and Dopamine Neuron Loss in a Presymptomatic Animal Model of Parkinson's Disease</title><author>Haik, Kristi L ; Shear, Deborah A ; Hargrove, Chad ; Patton, Jared ; Mazei-Robison, Michelle ; Sandstrom, Michael I ; Dunbar, Gary L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a393t-63bb96880a459e38df2e0267b25b316b96a700e30dde39f4806175e0309b33f63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Analysis of Variance</topic><topic>Animal</topic><topic>Animal Models</topic><topic>Animals</topic><topic>Behavior, Animal - drug effects</topic><topic>Disease Models, Animal</topic><topic>Dopamine</topic><topic>Dopamine - metabolism</topic><topic>Indazoles - therapeutic use</topic><topic>Learning Disorders - chemically induced</topic><topic>Learning Disorders - drug therapy</topic><topic>Learning Disorders - pathology</topic><topic>Male</topic><topic>Maze Learning - drug effects</topic><topic>NADP - metabolism</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>Neuroprotective Agents - therapeutic use</topic><topic>Oxidopamine</topic><topic>Parkinson Disease - drug therapy</topic><topic>Parkinson's Disease</topic><topic>Psychomotor Performance - drug effects</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Spatial Behavior - drug effects</topic><topic>Spatial Behavior - physiology</topic><topic>Spatial Learning</topic><topic>Substantia Nigra - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Haik, Kristi L</creatorcontrib><creatorcontrib>Shear, Deborah A</creatorcontrib><creatorcontrib>Hargrove, Chad</creatorcontrib><creatorcontrib>Patton, Jared</creatorcontrib><creatorcontrib>Mazei-Robison, Michelle</creatorcontrib><creatorcontrib>Sandstrom, Michael I</creatorcontrib><creatorcontrib>Dunbar, Gary L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PsycArticles (via ProQuest)</collection><collection>ProQuest One Psychology</collection><jtitle>Experimental and clinical psychopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Haik, Kristi L</au><au>Shear, Deborah A</au><au>Hargrove, Chad</au><au>Patton, Jared</au><au>Mazei-Robison, Michelle</au><au>Sandstrom, Michael I</au><au>Dunbar, Gary L</au><au>Mello, Nancy K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>7-Nitroindazole Attenuates 6-Hydroxydopamine-Induced Spatial Learning Deficits and Dopamine Neuron Loss in a Presymptomatic Animal Model of Parkinson's Disease</atitle><jtitle>Experimental and clinical psychopharmacology</jtitle><addtitle>Exp Clin Psychopharmacol</addtitle><date>2008-04</date><risdate>2008</risdate><volume>16</volume><issue>2</issue><spage>178</spage><epage>189</epage><pages>178-189</pages><issn>1064-1297</issn><eissn>1936-2293</eissn><abstract>Parkinson's disease (PD) is a neurodegenerative disorder in which loss of dopaminergic (DA) neurons (>50%) in the substantia nigra (SN) precede most of the overt motor symptoms, making early diagnosis and treatment interventions difficult. Because PD has been associated with free radicals generated by nitric oxide, this study tested whether treatments of 7-nitroindazole (7NI), a nitric-oxide-synthase inhibitor, could reduce cognitive deficits that often emerge before overt motor symptoms in a presymptomatic rat model of PD. Rats were given intraperitoneal injections of 50 mg/kg 7NI (or vehicle) just before receiving bilateral, intrastriatal injections of the DA-toxin, 6-hydroxydopamine (6-OHDA). The rats were then given a battery of motor tasks, and their learning ability was assessed using a spatial reversal task in a water-
T
maze. Results indicate that 7NI treatments attenuate 6-OHDA-induced spatial learning deficits and protect against DA cell loss in the SN, suggesting that 7NI may have potential as an early, presymptomatic pharmacotherapy for PD.</abstract><cop>United States</cop><pub>American Psychological Association</pub><pmid>18489022</pmid><doi>10.1037/1064-1297.16.2.178</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-2372-1420</orcidid></addata></record> |
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| subjects | Analysis of Variance Animal Animal Models Animals Behavior, Animal - drug effects Disease Models, Animal Dopamine Dopamine - metabolism Indazoles - therapeutic use Learning Disorders - chemically induced Learning Disorders - drug therapy Learning Disorders - pathology Male Maze Learning - drug effects NADP - metabolism Neurons - drug effects Neurons - metabolism Neuroprotective Agents - therapeutic use Oxidopamine Parkinson Disease - drug therapy Parkinson's Disease Psychomotor Performance - drug effects Rats Rats, Sprague-Dawley Spatial Behavior - drug effects Spatial Behavior - physiology Spatial Learning Substantia Nigra - pathology |
| title | 7-Nitroindazole Attenuates 6-Hydroxydopamine-Induced Spatial Learning Deficits and Dopamine Neuron Loss in a Presymptomatic Animal Model of Parkinson's Disease |
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