Effect of two noncompetitive AMPA receptor antagonists GYKI 52466 and GYKI 53405 on vigilance, behavior and spike–wave discharges in a genetic rat model of absence epilepsy
The present study was conducted to investigate the effects of two noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists, GYKI 52466 and GYKI 53405 (the racemate of talampanel) on the generation of spike–wave discharges (SWD) parallel with the vigilance a...
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| Veröffentlicht in: | Brain research 2004-05, Vol.1008 (2), p.236-244 |
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| creator | Jakus, Rita Graf, Marton Ando, Romeo D Balogh, Brigitta Gacsalyi, Istvan Levay, Gyorgy Kantor, Sandor Bagdy, Gyorgy |
| description | The present study was conducted to investigate the effects of two noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists, GYKI 52466 and GYKI 53405 (the racemate of talampanel) on the generation of spike–wave discharges (SWD) parallel with the vigilance and behavioral changes in the genetic absence epilepsy model of WAG/Rij rats. Intraperitoneal (i.p.) administration of GYKI 52466 (1-[4-aminophenyl]-4-methyl-7,8-methylenedioxy-5
H-2,3-benzodiazepine; 3, 10 and 30 mg/kg, i.p.), the prototypic compound of the 2,3-benzodiazepine family, caused a fast dose-dependent increase in the number and cumulative duration of SWD. These changes were accompanied by dose-dependent increase in duration of light slow wave sleep (SWS1) and passive awake, vigilance states associated with the presence of SWD. In addition a short, transient behavioral activation occurred that was followed by strong ataxia and immobility, decrease of active wakefulness and increase in deep slow wave sleep. GYKI 53405 (7-acetyl-5-(4-aminophenyl)-8-methyl-8,9-dihydro-7
H-1,3-dioxolo[4,5-b][2,3]benzodiazepine, the racemate of talampanel, 16 mg/kg, i.p.) failed to affect any measure of SWD and vigilance. When used as a pretreatment, GYKI 52466 (10 mg/kg) slightly attenuated SWD-promoting effects of the 5-HT
1A receptor agonist 8-OH-DPAT, it decreased cumulative duration and average time of paroxysms. In conclusion, AMPA receptors play moderate role in regulation of epileptic activity, and some of these effects are connected to their effects on vigilance in this model. |
| doi_str_mv | 10.1016/j.brainres.2004.01.087 |
| format | Article |
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H-2,3-benzodiazepine; 3, 10 and 30 mg/kg, i.p.), the prototypic compound of the 2,3-benzodiazepine family, caused a fast dose-dependent increase in the number and cumulative duration of SWD. These changes were accompanied by dose-dependent increase in duration of light slow wave sleep (SWS1) and passive awake, vigilance states associated with the presence of SWD. In addition a short, transient behavioral activation occurred that was followed by strong ataxia and immobility, decrease of active wakefulness and increase in deep slow wave sleep. GYKI 53405 (7-acetyl-5-(4-aminophenyl)-8-methyl-8,9-dihydro-7
H-1,3-dioxolo[4,5-b][2,3]benzodiazepine, the racemate of talampanel, 16 mg/kg, i.p.) failed to affect any measure of SWD and vigilance. When used as a pretreatment, GYKI 52466 (10 mg/kg) slightly attenuated SWD-promoting effects of the 5-HT
1A receptor agonist 8-OH-DPAT, it decreased cumulative duration and average time of paroxysms. In conclusion, AMPA receptors play moderate role in regulation of epileptic activity, and some of these effects are connected to their effects on vigilance in this model.</description><identifier>ISSN: 0006-8993</identifier><identifier>EISSN: 1872-6240</identifier><identifier>DOI: 10.1016/j.brainres.2004.01.087</identifier><identifier>PMID: 15145761</identifier><identifier>CODEN: BRREAP</identifier><language>eng</language><publisher>London: Elsevier B.V</publisher><subject>5-HT 1A receptor ; 8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology ; Absence epilepsy ; AMPA receptor ; Animals ; Arousal - drug effects ; Behavior, Animal - drug effects ; Benzodiazepines - pharmacology ; Biological and medical sciences ; Dose-Response Relationship, Drug ; Electroencephalography ; Electromyography ; Epilepsy, Absence - genetics ; Epilepsy, Absence - physiopathology ; Epilepsy, Absence - psychology ; Excitatory Amino Acid Antagonists - pharmacology ; Glutamate ; GYKI 52466 ; GYKI 53405 ; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy ; Male ; Medical sciences ; Nervous system (semeiology, syndromes) ; Neurology ; Rats ; Receptors, AMPA - antagonists & inhibitors ; Serotonin ; Serotonin Receptor Agonists - pharmacology ; Sleep ; Sleep - drug effects ; Spike–wave discharge ; Talampanel ; Wakefulness - drug effects</subject><ispartof>Brain research, 2004-05, Vol.1008 (2), p.236-244</ispartof><rights>2004 Elsevier B.V.</rights><rights>2004 INIST-CNRS</rights><rights>Copyright 2004 Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c425t-645fd50cc6e583649bb6c2b7abce93f4352694dc29e1e835559f266e886d9b333</citedby><cites>FETCH-LOGICAL-c425t-645fd50cc6e583649bb6c2b7abce93f4352694dc29e1e835559f266e886d9b333</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006899304003269$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15778854$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15145761$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jakus, Rita</creatorcontrib><creatorcontrib>Graf, Marton</creatorcontrib><creatorcontrib>Ando, Romeo D</creatorcontrib><creatorcontrib>Balogh, Brigitta</creatorcontrib><creatorcontrib>Gacsalyi, Istvan</creatorcontrib><creatorcontrib>Levay, Gyorgy</creatorcontrib><creatorcontrib>Kantor, Sandor</creatorcontrib><creatorcontrib>Bagdy, Gyorgy</creatorcontrib><title>Effect of two noncompetitive AMPA receptor antagonists GYKI 52466 and GYKI 53405 on vigilance, behavior and spike–wave discharges in a genetic rat model of absence epilepsy</title><title>Brain research</title><addtitle>Brain Res</addtitle><description>The present study was conducted to investigate the effects of two noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists, GYKI 52466 and GYKI 53405 (the racemate of talampanel) on the generation of spike–wave discharges (SWD) parallel with the vigilance and behavioral changes in the genetic absence epilepsy model of WAG/Rij rats. Intraperitoneal (i.p.) administration of GYKI 52466 (1-[4-aminophenyl]-4-methyl-7,8-methylenedioxy-5
H-2,3-benzodiazepine; 3, 10 and 30 mg/kg, i.p.), the prototypic compound of the 2,3-benzodiazepine family, caused a fast dose-dependent increase in the number and cumulative duration of SWD. These changes were accompanied by dose-dependent increase in duration of light slow wave sleep (SWS1) and passive awake, vigilance states associated with the presence of SWD. In addition a short, transient behavioral activation occurred that was followed by strong ataxia and immobility, decrease of active wakefulness and increase in deep slow wave sleep. GYKI 53405 (7-acetyl-5-(4-aminophenyl)-8-methyl-8,9-dihydro-7
H-1,3-dioxolo[4,5-b][2,3]benzodiazepine, the racemate of talampanel, 16 mg/kg, i.p.) failed to affect any measure of SWD and vigilance. When used as a pretreatment, GYKI 52466 (10 mg/kg) slightly attenuated SWD-promoting effects of the 5-HT
1A receptor agonist 8-OH-DPAT, it decreased cumulative duration and average time of paroxysms. In conclusion, AMPA receptors play moderate role in regulation of epileptic activity, and some of these effects are connected to their effects on vigilance in this model.</description><subject>5-HT 1A receptor</subject><subject>8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology</subject><subject>Absence epilepsy</subject><subject>AMPA receptor</subject><subject>Animals</subject><subject>Arousal - drug effects</subject><subject>Behavior, Animal - drug effects</subject><subject>Benzodiazepines - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Dose-Response Relationship, Drug</subject><subject>Electroencephalography</subject><subject>Electromyography</subject><subject>Epilepsy, Absence - genetics</subject><subject>Epilepsy, Absence - physiopathology</subject><subject>Epilepsy, Absence - psychology</subject><subject>Excitatory Amino Acid Antagonists - pharmacology</subject><subject>Glutamate</subject><subject>GYKI 52466</subject><subject>GYKI 53405</subject><subject>Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Nervous system (semeiology, syndromes)</subject><subject>Neurology</subject><subject>Rats</subject><subject>Receptors, AMPA - antagonists & inhibitors</subject><subject>Serotonin</subject><subject>Serotonin Receptor Agonists - pharmacology</subject><subject>Sleep</subject><subject>Sleep - drug effects</subject><subject>Spike–wave discharge</subject><subject>Talampanel</subject><subject>Wakefulness - drug effects</subject><issn>0006-8993</issn><issn>1872-6240</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9u1DAQxi0EokvhFSpf4NQEO_6T5MaqKqWiCA5w4GQ59mTrJYmD7d2qN96B9-CheBK8bBDcOFlj_eabme9D6IySkhIqX27LLmg3BYhlRQgvCS1JUz9AK9rUVSErTh6iFSFEFk3bshP0JMZtLhlryWN0QgXlopZ0hX5c9j2YhH2P053Hk5-MH2dILrk94PW7D2scwMCcfMB6SnrjJxdTxFef315jUXEp87ddSsaJwH7Ce7dxg54MnOMObvXe_W62OM7uC_z89v1OZ23rornVYQMRuwlrvIEpjzU46IRHb2E47KS7CFkHw-wGmOP9U_So10OEZ8t7ij69vvx48aa4eX91fbG-KQyvRCokF70VxBgJomGSt10nTdXVujPQsp4zUcmWW1O1QKFhQoi2r6SEppG27Rhjp-jFUXcO_usOYlJjXheGfBX4XVS0rmlNmcygPIIm-BgD9GoObtThXlGiDkmprfqTlDokpQhVOanceLZM2HUj2L9tSzQZeL4AOho99CEb6uI_XF03jeCZe3XkIPuxdxBUNO5gmnU5uaSsd__b5RffB7Y9</recordid><startdate>20040522</startdate><enddate>20040522</enddate><creator>Jakus, Rita</creator><creator>Graf, Marton</creator><creator>Ando, Romeo D</creator><creator>Balogh, Brigitta</creator><creator>Gacsalyi, Istvan</creator><creator>Levay, Gyorgy</creator><creator>Kantor, Sandor</creator><creator>Bagdy, Gyorgy</creator><general>Elsevier B.V</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>7TK</scope></search><sort><creationdate>20040522</creationdate><title>Effect of two noncompetitive AMPA receptor antagonists GYKI 52466 and GYKI 53405 on vigilance, behavior and spike–wave discharges in a genetic rat model of absence epilepsy</title><author>Jakus, Rita ; Graf, Marton ; Ando, Romeo D ; Balogh, Brigitta ; Gacsalyi, Istvan ; Levay, Gyorgy ; Kantor, Sandor ; Bagdy, Gyorgy</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c425t-645fd50cc6e583649bb6c2b7abce93f4352694dc29e1e835559f266e886d9b333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>5-HT 1A receptor</topic><topic>8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology</topic><topic>Absence epilepsy</topic><topic>AMPA receptor</topic><topic>Animals</topic><topic>Arousal - drug effects</topic><topic>Behavior, Animal - drug effects</topic><topic>Benzodiazepines - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Dose-Response Relationship, Drug</topic><topic>Electroencephalography</topic><topic>Electromyography</topic><topic>Epilepsy, Absence - genetics</topic><topic>Epilepsy, Absence - physiopathology</topic><topic>Epilepsy, Absence - psychology</topic><topic>Excitatory Amino Acid Antagonists - pharmacology</topic><topic>Glutamate</topic><topic>GYKI 52466</topic><topic>GYKI 53405</topic><topic>Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Nervous system (semeiology, syndromes)</topic><topic>Neurology</topic><topic>Rats</topic><topic>Receptors, AMPA - antagonists & inhibitors</topic><topic>Serotonin</topic><topic>Serotonin Receptor Agonists - pharmacology</topic><topic>Sleep</topic><topic>Sleep - drug effects</topic><topic>Spike–wave discharge</topic><topic>Talampanel</topic><topic>Wakefulness - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jakus, Rita</creatorcontrib><creatorcontrib>Graf, Marton</creatorcontrib><creatorcontrib>Ando, Romeo D</creatorcontrib><creatorcontrib>Balogh, Brigitta</creatorcontrib><creatorcontrib>Gacsalyi, Istvan</creatorcontrib><creatorcontrib>Levay, Gyorgy</creatorcontrib><creatorcontrib>Kantor, Sandor</creatorcontrib><creatorcontrib>Bagdy, Gyorgy</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>Brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jakus, Rita</au><au>Graf, Marton</au><au>Ando, Romeo D</au><au>Balogh, Brigitta</au><au>Gacsalyi, Istvan</au><au>Levay, Gyorgy</au><au>Kantor, Sandor</au><au>Bagdy, Gyorgy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of two noncompetitive AMPA receptor antagonists GYKI 52466 and GYKI 53405 on vigilance, behavior and spike–wave discharges in a genetic rat model of absence epilepsy</atitle><jtitle>Brain research</jtitle><addtitle>Brain Res</addtitle><date>2004-05-22</date><risdate>2004</risdate><volume>1008</volume><issue>2</issue><spage>236</spage><epage>244</epage><pages>236-244</pages><issn>0006-8993</issn><eissn>1872-6240</eissn><coden>BRREAP</coden><abstract>The present study was conducted to investigate the effects of two noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists, GYKI 52466 and GYKI 53405 (the racemate of talampanel) on the generation of spike–wave discharges (SWD) parallel with the vigilance and behavioral changes in the genetic absence epilepsy model of WAG/Rij rats. Intraperitoneal (i.p.) administration of GYKI 52466 (1-[4-aminophenyl]-4-methyl-7,8-methylenedioxy-5
H-2,3-benzodiazepine; 3, 10 and 30 mg/kg, i.p.), the prototypic compound of the 2,3-benzodiazepine family, caused a fast dose-dependent increase in the number and cumulative duration of SWD. These changes were accompanied by dose-dependent increase in duration of light slow wave sleep (SWS1) and passive awake, vigilance states associated with the presence of SWD. In addition a short, transient behavioral activation occurred that was followed by strong ataxia and immobility, decrease of active wakefulness and increase in deep slow wave sleep. GYKI 53405 (7-acetyl-5-(4-aminophenyl)-8-methyl-8,9-dihydro-7
H-1,3-dioxolo[4,5-b][2,3]benzodiazepine, the racemate of talampanel, 16 mg/kg, i.p.) failed to affect any measure of SWD and vigilance. When used as a pretreatment, GYKI 52466 (10 mg/kg) slightly attenuated SWD-promoting effects of the 5-HT
1A receptor agonist 8-OH-DPAT, it decreased cumulative duration and average time of paroxysms. In conclusion, AMPA receptors play moderate role in regulation of epileptic activity, and some of these effects are connected to their effects on vigilance in this model.</abstract><cop>London</cop><cop>Amsterdam</cop><cop>New York, NY</cop><pub>Elsevier B.V</pub><pmid>15145761</pmid><doi>10.1016/j.brainres.2004.01.087</doi><tpages>9</tpages></addata></record> |
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| subjects | 5-HT 1A receptor 8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology Absence epilepsy AMPA receptor Animals Arousal - drug effects Behavior, Animal - drug effects Benzodiazepines - pharmacology Biological and medical sciences Dose-Response Relationship, Drug Electroencephalography Electromyography Epilepsy, Absence - genetics Epilepsy, Absence - physiopathology Epilepsy, Absence - psychology Excitatory Amino Acid Antagonists - pharmacology Glutamate GYKI 52466 GYKI 53405 Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy Male Medical sciences Nervous system (semeiology, syndromes) Neurology Rats Receptors, AMPA - antagonists & inhibitors Serotonin Serotonin Receptor Agonists - pharmacology Sleep Sleep - drug effects Spike–wave discharge Talampanel Wakefulness - drug effects |
| title | Effect of two noncompetitive AMPA receptor antagonists GYKI 52466 and GYKI 53405 on vigilance, behavior and spike–wave discharges in a genetic rat model of absence epilepsy |
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