N‐tert‐butyl‐alpha‐phenylnitrone, a free radical scavenger with anticholinesterase activity does not improve the cognitive performance of scopolamine‐challenged rats
Reversible inhibitors of acetylcholinesterase improve spatial learning and memory in animal models of cognitive impairment. Here we investigate if the beneficial effects of free radical scavenger N‐tert‐butyl‐alpha‐phenylnitrone (PBN) on cognitive performance could be explained by its recently disco...
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| Veröffentlicht in: | International journal of developmental neuroscience 2001-06, Vol.19 (3), p.319-325 |
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| container_title | International journal of developmental neuroscience |
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| creator | Milivojevic, Nataša Babic, Ksenja Milatovic, Dejan Dettbarn, Wolf‐D. Sket, Dusan Zivin, Marko |
| description | Reversible inhibitors of acetylcholinesterase improve spatial learning and memory in animal models of cognitive impairment. Here we investigate if the beneficial effects of free radical scavenger N‐tert‐butyl‐alpha‐phenylnitrone (PBN) on cognitive performance could be explained by its recently discovered anticholinesterase activity. Morris water maze experiment was performed to examine the effect of PBN on the impairment of spatial learning and memory induced by the antagonist of cholinergic muscarinic transmission scopolamine. In situ hybridization histochemistry experiment was performed to study its effects on the induction of immediate early gene expression (c‐fos, c‐jun) by dopamine D1 receptor agonist SKF‐82958 and on the augmentation of the SKF‐82958‐induced expression of these genes by scopolamine. In both experiments, the effects of PBN were compared to the effects of reversible anticholinesterase physostigmine. We found that physostigmine but not PBN significantly reversed the cognitive impairment in scopolamine‐challenged rats, prevented the induction of c‐fos and c‐jun mRNAs by SKF‐82958 and attenuated the augmentation of the SKF‐82958‐induced expression of these genes by scopolamine. The present experiments did not reveal a significant in vivo anticholinesterase activity of PBN. |
| doi_str_mv | 10.1016/S0736-5748(01)00016-8 |
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Here we investigate if the beneficial effects of free radical scavenger N‐tert‐butyl‐alpha‐phenylnitrone (PBN) on cognitive performance could be explained by its recently discovered anticholinesterase activity. Morris water maze experiment was performed to examine the effect of PBN on the impairment of spatial learning and memory induced by the antagonist of cholinergic muscarinic transmission scopolamine. In situ hybridization histochemistry experiment was performed to study its effects on the induction of immediate early gene expression (c‐fos, c‐jun) by dopamine D1 receptor agonist SKF‐82958 and on the augmentation of the SKF‐82958‐induced expression of these genes by scopolamine. In both experiments, the effects of PBN were compared to the effects of reversible anticholinesterase physostigmine. We found that physostigmine but not PBN significantly reversed the cognitive impairment in scopolamine‐challenged rats, prevented the induction of c‐fos and c‐jun mRNAs by SKF‐82958 and attenuated the augmentation of the SKF‐82958‐induced expression of these genes by scopolamine. The present experiments did not reveal a significant in vivo anticholinesterase activity of PBN.</description><identifier>ISSN: 0736-5748</identifier><identifier>EISSN: 1873-474X</identifier><identifier>DOI: 10.1016/S0736-5748(01)00016-8</identifier><identifier>PMID: 11337201</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Anticholinesterase activity ; Benzazepines - pharmacology ; Cholinesterase Inhibitors - pharmacology ; Cognition - drug effects ; Cyclic N-Oxides ; Dopamine Agonists - pharmacology ; Free radical scavenger ; Free Radical Scavengers - pharmacology ; Gene Expression - drug effects ; Genes, Immediate-Early - drug effects ; Male ; Maze Learning - drug effects ; Memory - drug effects ; Muscarinic Antagonists - pharmacology ; N-tert-^AButyl-alpha-phenylnitrone ; Nitrogen Oxides - pharmacology ; Physostigmine - pharmacology ; Proto-Oncogene Proteins c-fos - genetics ; Proto-Oncogene Proteins c-jun - genetics ; Rats ; Rats, Wistar ; scopolamine ; Scopolamine - pharmacology ; Scopolamine‐challenged rats ; Space Perception - drug effects</subject><ispartof>International journal of developmental neuroscience, 2001-06, Vol.19 (3), p.319-325</ispartof><rights>2001 ISDN</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4008-3c7ba842cb602494cef4a0a944b983a640f7c6a43ee75934b65b6c31b1226ae73</citedby><cites>FETCH-LOGICAL-c4008-3c7ba842cb602494cef4a0a944b983a640f7c6a43ee75934b65b6c31b1226ae73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1016%2FS0736-5748%2801%2900016-8$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1016%2FS0736-5748%2801%2900016-8$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11337201$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Milivojevic, Nataša</creatorcontrib><creatorcontrib>Babic, Ksenja</creatorcontrib><creatorcontrib>Milatovic, Dejan</creatorcontrib><creatorcontrib>Dettbarn, Wolf‐D.</creatorcontrib><creatorcontrib>Sket, Dusan</creatorcontrib><creatorcontrib>Zivin, Marko</creatorcontrib><title>N‐tert‐butyl‐alpha‐phenylnitrone, a free radical scavenger with anticholinesterase activity does not improve the cognitive performance of scopolamine‐challenged rats</title><title>International journal of developmental neuroscience</title><addtitle>Int J Dev Neurosci</addtitle><description>Reversible inhibitors of acetylcholinesterase improve spatial learning and memory in animal models of cognitive impairment. Here we investigate if the beneficial effects of free radical scavenger N‐tert‐butyl‐alpha‐phenylnitrone (PBN) on cognitive performance could be explained by its recently discovered anticholinesterase activity. Morris water maze experiment was performed to examine the effect of PBN on the impairment of spatial learning and memory induced by the antagonist of cholinergic muscarinic transmission scopolamine. In situ hybridization histochemistry experiment was performed to study its effects on the induction of immediate early gene expression (c‐fos, c‐jun) by dopamine D1 receptor agonist SKF‐82958 and on the augmentation of the SKF‐82958‐induced expression of these genes by scopolamine. In both experiments, the effects of PBN were compared to the effects of reversible anticholinesterase physostigmine. We found that physostigmine but not PBN significantly reversed the cognitive impairment in scopolamine‐challenged rats, prevented the induction of c‐fos and c‐jun mRNAs by SKF‐82958 and attenuated the augmentation of the SKF‐82958‐induced expression of these genes by scopolamine. The present experiments did not reveal a significant in vivo anticholinesterase activity of PBN.</description><subject>Animals</subject><subject>Anticholinesterase activity</subject><subject>Benzazepines - pharmacology</subject><subject>Cholinesterase Inhibitors - pharmacology</subject><subject>Cognition - drug effects</subject><subject>Cyclic N-Oxides</subject><subject>Dopamine Agonists - pharmacology</subject><subject>Free radical scavenger</subject><subject>Free Radical Scavengers - pharmacology</subject><subject>Gene Expression - drug effects</subject><subject>Genes, Immediate-Early - drug effects</subject><subject>Male</subject><subject>Maze Learning - drug effects</subject><subject>Memory - drug effects</subject><subject>Muscarinic Antagonists - pharmacology</subject><subject>N-tert-^AButyl-alpha-phenylnitrone</subject><subject>Nitrogen Oxides - pharmacology</subject><subject>Physostigmine - pharmacology</subject><subject>Proto-Oncogene Proteins c-fos - genetics</subject><subject>Proto-Oncogene Proteins c-jun - genetics</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>scopolamine</subject><subject>Scopolamine - pharmacology</subject><subject>Scopolamine‐challenged rats</subject><subject>Space Perception - drug effects</subject><issn>0736-5748</issn><issn>1873-474X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkcFu1DAQhiMEotvCI4B8QiARsGMn9h5RgQKqygGQuFkT76QxcuJge7fKrY_Am_BOPAnO7gqOcPrlmX--GesvikeMvmCUNS8_UcmbspZCPaXsGaW5Vqo7xYopyUshxde7xeqP5aQ4jfFbNtU1FfeLE8Y4lxVlq-Ln1a_bHwlDytJu0-yygpt6yDr1OM5utCn4EZ8TIF1AJAE21oAj0cAOx2sM5MamnsCYrOm9syPGzIOIBEyyO5tmsvEYyegTscMU_A5J6pEYf53RNr8mDJ0PA4wGie8y2E_ewZBJ-QjTg3PLnk3enOKD4l4HLuLDo54VX96--Xz-rrz8ePH-_NVlaQSlquRGtqBEZdqGVmItDHYCKKyFaNeKQyNoJ00DgiPKes1F29RtYzhrWVU1gJKfFU8O3Hzw923-kh5sNOgcjOi3UUuqWCWb6p9GpqiiDVuI9cFogo8xYKenYAcIs2ZUL5HqfaR6yUtTpveRapXnHh8XbNsBN3-njhlmw8XBcGMdzv9H1R9eX-0bS52yfVXx3whbugs</recordid><startdate>200106</startdate><enddate>200106</enddate><creator>Milivojevic, Nataša</creator><creator>Babic, Ksenja</creator><creator>Milatovic, Dejan</creator><creator>Dettbarn, Wolf‐D.</creator><creator>Sket, Dusan</creator><creator>Zivin, Marko</creator><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><scope>7X8</scope></search><sort><creationdate>200106</creationdate><title>N‐tert‐butyl‐alpha‐phenylnitrone, a free radical scavenger with anticholinesterase activity does not improve the cognitive performance of scopolamine‐challenged rats</title><author>Milivojevic, Nataša ; Babic, Ksenja ; Milatovic, Dejan ; Dettbarn, Wolf‐D. ; Sket, Dusan ; Zivin, Marko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4008-3c7ba842cb602494cef4a0a944b983a640f7c6a43ee75934b65b6c31b1226ae73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>Anticholinesterase activity</topic><topic>Benzazepines - pharmacology</topic><topic>Cholinesterase Inhibitors - pharmacology</topic><topic>Cognition - drug effects</topic><topic>Cyclic N-Oxides</topic><topic>Dopamine Agonists - pharmacology</topic><topic>Free radical scavenger</topic><topic>Free Radical Scavengers - pharmacology</topic><topic>Gene Expression - drug effects</topic><topic>Genes, Immediate-Early - drug effects</topic><topic>Male</topic><topic>Maze Learning - drug effects</topic><topic>Memory - drug effects</topic><topic>Muscarinic Antagonists - pharmacology</topic><topic>N-tert-^AButyl-alpha-phenylnitrone</topic><topic>Nitrogen Oxides - pharmacology</topic><topic>Physostigmine - pharmacology</topic><topic>Proto-Oncogene Proteins c-fos - genetics</topic><topic>Proto-Oncogene Proteins c-jun - genetics</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>scopolamine</topic><topic>Scopolamine - pharmacology</topic><topic>Scopolamine‐challenged rats</topic><topic>Space Perception - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Milivojevic, Nataša</creatorcontrib><creatorcontrib>Babic, Ksenja</creatorcontrib><creatorcontrib>Milatovic, Dejan</creatorcontrib><creatorcontrib>Dettbarn, Wolf‐D.</creatorcontrib><creatorcontrib>Sket, Dusan</creatorcontrib><creatorcontrib>Zivin, Marko</creatorcontrib><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><collection>MEDLINE - Academic</collection><jtitle>International journal of developmental neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Milivojevic, Nataša</au><au>Babic, Ksenja</au><au>Milatovic, Dejan</au><au>Dettbarn, Wolf‐D.</au><au>Sket, Dusan</au><au>Zivin, Marko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>N‐tert‐butyl‐alpha‐phenylnitrone, a free radical scavenger with anticholinesterase activity does not improve the cognitive performance of scopolamine‐challenged rats</atitle><jtitle>International journal of developmental neuroscience</jtitle><addtitle>Int J Dev Neurosci</addtitle><date>2001-06</date><risdate>2001</risdate><volume>19</volume><issue>3</issue><spage>319</spage><epage>325</epage><pages>319-325</pages><issn>0736-5748</issn><eissn>1873-474X</eissn><abstract>Reversible inhibitors of acetylcholinesterase improve spatial learning and memory in animal models of cognitive impairment. Here we investigate if the beneficial effects of free radical scavenger N‐tert‐butyl‐alpha‐phenylnitrone (PBN) on cognitive performance could be explained by its recently discovered anticholinesterase activity. Morris water maze experiment was performed to examine the effect of PBN on the impairment of spatial learning and memory induced by the antagonist of cholinergic muscarinic transmission scopolamine. In situ hybridization histochemistry experiment was performed to study its effects on the induction of immediate early gene expression (c‐fos, c‐jun) by dopamine D1 receptor agonist SKF‐82958 and on the augmentation of the SKF‐82958‐induced expression of these genes by scopolamine. In both experiments, the effects of PBN were compared to the effects of reversible anticholinesterase physostigmine. We found that physostigmine but not PBN significantly reversed the cognitive impairment in scopolamine‐challenged rats, prevented the induction of c‐fos and c‐jun mRNAs by SKF‐82958 and attenuated the augmentation of the SKF‐82958‐induced expression of these genes by scopolamine. The present experiments did not reveal a significant in vivo anticholinesterase activity of PBN.</abstract><cop>United States</cop><pmid>11337201</pmid><doi>10.1016/S0736-5748(01)00016-8</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | International journal of developmental neuroscience, 2001-06, Vol.19 (3), p.319-325 |
| issn | 0736-5748 1873-474X |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Elsevier ScienceDirect Journals |
| subjects | Animals Anticholinesterase activity Benzazepines - pharmacology Cholinesterase Inhibitors - pharmacology Cognition - drug effects Cyclic N-Oxides Dopamine Agonists - pharmacology Free radical scavenger Free Radical Scavengers - pharmacology Gene Expression - drug effects Genes, Immediate-Early - drug effects Male Maze Learning - drug effects Memory - drug effects Muscarinic Antagonists - pharmacology N-tert-^AButyl-alpha-phenylnitrone Nitrogen Oxides - pharmacology Physostigmine - pharmacology Proto-Oncogene Proteins c-fos - genetics Proto-Oncogene Proteins c-jun - genetics Rats Rats, Wistar scopolamine Scopolamine - pharmacology Scopolamine‐challenged rats Space Perception - drug effects |
| title | N‐tert‐butyl‐alpha‐phenylnitrone, a free radical scavenger with anticholinesterase activity does not improve the cognitive performance of scopolamine‐challenged rats |
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