Antagonism of picrotoxin-induced changes in dopamine and serotonin metabolism by allopregnanolone and midazolam
The effects of allopregnanolone and midazolam, given intracerebroventricularly, on the behavioral and biochemical effects of picrotoxin, were examined in a model of neurotoxin-induced seizures, in mice. After acute injections, midazolam (ED 50=39.8 nmol) and allopregnanolone (ED 50=11.0 nmol) produc...
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| Veröffentlicht in: | Pharmacology, biochemistry and behavior biochemistry and behavior, 2002-07, Vol.72 (4), p.987-991 |
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| creator | Maciejak, Piotr Krząścik, Paweł Członkowska, Agnieszka I. Szyndler, Janusz Bidziński, Andrzej Walkowiak, Jerzy Kostowski, Wojciech Plaznik, Adam |
| description | The effects of allopregnanolone and midazolam, given intracerebroventricularly, on the behavioral and biochemical effects of picrotoxin, were examined in a model of neurotoxin-induced seizures, in mice. After acute injections, midazolam (ED
50=39.8 nmol) and allopregnanolone (ED
50=11.0 nmol) produced similar and dose-dependent protection against picrotoxin-induced seizures. Picrotoxin given intraperitoneally at the ED
85 dose decreased significantly the concentration of serotonin (5-HT), dopamine (DA), homovanilic acid (HVA) and 3,4-dihydroxyindolacetic acid (DOPAC), in the mouse striatum and the frontal cortex, in the period of time immediately preceding the onset of seizures. A single injection of allopregnanolone more potently, in comparison to midazolam, antagonized the biochemical action of picrotoxin, abolishing its effects on DA, HVA and 5-HT concentration, in the mouse striatum and the frontal cortex. These results for the first time provide a direct argument for an involvement of central dopaminergic and serotonergic systems in the seizure development. The present data add also to the accumulating evidence suggesting a favorable pharmacological profile for some neurosteroids currently considered to have a future role in the management of epilepsy. |
| doi_str_mv | 10.1016/S0091-3057(02)00811-0 |
| format | Article |
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50=39.8 nmol) and allopregnanolone (ED
50=11.0 nmol) produced similar and dose-dependent protection against picrotoxin-induced seizures. Picrotoxin given intraperitoneally at the ED
85 dose decreased significantly the concentration of serotonin (5-HT), dopamine (DA), homovanilic acid (HVA) and 3,4-dihydroxyindolacetic acid (DOPAC), in the mouse striatum and the frontal cortex, in the period of time immediately preceding the onset of seizures. A single injection of allopregnanolone more potently, in comparison to midazolam, antagonized the biochemical action of picrotoxin, abolishing its effects on DA, HVA and 5-HT concentration, in the mouse striatum and the frontal cortex. These results for the first time provide a direct argument for an involvement of central dopaminergic and serotonergic systems in the seizure development. The present data add also to the accumulating evidence suggesting a favorable pharmacological profile for some neurosteroids currently considered to have a future role in the management of epilepsy.</description><identifier>ISSN: 0091-3057</identifier><identifier>EISSN: 1873-5177</identifier><identifier>DOI: 10.1016/S0091-3057(02)00811-0</identifier><identifier>PMID: 12062590</identifier><identifier>CODEN: PBBHAU</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Allopregnanolone ; Amino Acids - metabolism ; Animals ; Anticonvulsants. Antiepileptics. Antiparkinson agents ; Biological and medical sciences ; Convulsants - pharmacology ; Dopamine ; Dopamine - metabolism ; Dose-Response Relationship, Drug ; GABA Antagonists - pharmacology ; GABA Modulators - pharmacology ; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy ; Injections, Intraventricular ; Intracerebroventricular injections ; Intraperitoneal injections ; Male ; Medical sciences ; Mice ; Microinjections ; Midazolam ; Midazolam - pharmacology ; Nervous system (semeiology, syndromes) ; Neurology ; Neuropharmacology ; Pharmacology. Drug treatments ; Picrotoxin ; Picrotoxin - antagonists & inhibitors ; Picrotoxin - pharmacology ; Pregnanolone - pharmacology ; Seizures ; Seizures - chemically induced ; Seizures - psychology ; Serotonin ; Serotonin - metabolism</subject><ispartof>Pharmacology, biochemistry and behavior, 2002-07, Vol.72 (4), p.987-991</ispartof><rights>2002 Elsevier Science Inc.</rights><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-ca65268945a5bdd2f37de45edd34524acbebbfe2bba82e1f2d147fd2f515c18f3</citedby><cites>FETCH-LOGICAL-c422t-ca65268945a5bdd2f37de45edd34524acbebbfe2bba82e1f2d147fd2f515c18f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0091-3057(02)00811-0$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13808245$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12062590$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Maciejak, Piotr</creatorcontrib><creatorcontrib>Krząścik, Paweł</creatorcontrib><creatorcontrib>Członkowska, Agnieszka I.</creatorcontrib><creatorcontrib>Szyndler, Janusz</creatorcontrib><creatorcontrib>Bidziński, Andrzej</creatorcontrib><creatorcontrib>Walkowiak, Jerzy</creatorcontrib><creatorcontrib>Kostowski, Wojciech</creatorcontrib><creatorcontrib>Plaznik, Adam</creatorcontrib><title>Antagonism of picrotoxin-induced changes in dopamine and serotonin metabolism by allopregnanolone and midazolam</title><title>Pharmacology, biochemistry and behavior</title><addtitle>Pharmacol Biochem Behav</addtitle><description>The effects of allopregnanolone and midazolam, given intracerebroventricularly, on the behavioral and biochemical effects of picrotoxin, were examined in a model of neurotoxin-induced seizures, in mice. After acute injections, midazolam (ED
50=39.8 nmol) and allopregnanolone (ED
50=11.0 nmol) produced similar and dose-dependent protection against picrotoxin-induced seizures. Picrotoxin given intraperitoneally at the ED
85 dose decreased significantly the concentration of serotonin (5-HT), dopamine (DA), homovanilic acid (HVA) and 3,4-dihydroxyindolacetic acid (DOPAC), in the mouse striatum and the frontal cortex, in the period of time immediately preceding the onset of seizures. A single injection of allopregnanolone more potently, in comparison to midazolam, antagonized the biochemical action of picrotoxin, abolishing its effects on DA, HVA and 5-HT concentration, in the mouse striatum and the frontal cortex. These results for the first time provide a direct argument for an involvement of central dopaminergic and serotonergic systems in the seizure development. The present data add also to the accumulating evidence suggesting a favorable pharmacological profile for some neurosteroids currently considered to have a future role in the management of epilepsy.</description><subject>Allopregnanolone</subject><subject>Amino Acids - metabolism</subject><subject>Animals</subject><subject>Anticonvulsants. Antiepileptics. Antiparkinson agents</subject><subject>Biological and medical sciences</subject><subject>Convulsants - pharmacology</subject><subject>Dopamine</subject><subject>Dopamine - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>GABA Antagonists - pharmacology</subject><subject>GABA Modulators - pharmacology</subject><subject>Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy</subject><subject>Injections, Intraventricular</subject><subject>Intracerebroventricular injections</subject><subject>Intraperitoneal injections</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Microinjections</subject><subject>Midazolam</subject><subject>Midazolam - pharmacology</subject><subject>Nervous system (semeiology, syndromes)</subject><subject>Neurology</subject><subject>Neuropharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Picrotoxin</subject><subject>Picrotoxin - antagonists & inhibitors</subject><subject>Picrotoxin - pharmacology</subject><subject>Pregnanolone - pharmacology</subject><subject>Seizures</subject><subject>Seizures - chemically induced</subject><subject>Seizures - psychology</subject><subject>Serotonin</subject><subject>Serotonin - metabolism</subject><issn>0091-3057</issn><issn>1873-5177</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0E1vFCEYwHFibOy2-hE0c9HoYSowMDN7Mk1j1aRJD-qZPMDDimFghFlj_fRluxN79ERCfg8vf0JeMnrBKOvff6V0y9qOyuEt5e8oHRlr6ROyYePQtZINw1Oy-UdOyVkpPymlgvfDM3LKOO253NINSZdxgV2KvkxNcs3sTU5L-uNj66PdG7SN-QFxh6XxsbFphslHbCDapuBBxro94QI6hcMR-q6BENKccRchppBWPHkLf1OA6Tk5cRAKvljXc_L9-uO3q8_tze2nL1eXN60RnC-tgV7yftwKCVJby103WBQSre2E5AKMRq0dcq1h5Mgct0wMrjrJpGGj687Jm-O5c06_9lgWNfliMASImPZFsVH0gvXbCuUR1o-XktGpOfsJ8p1iVB1Kq4fS6pBRUa4eSita516tF-z1hPZxak1bwesVQDEQXIZofHl03UhHLmR1H44Oa47fHrMqxmOs6X1Gsyib_H-ecg9a5J2q</recordid><startdate>20020701</startdate><enddate>20020701</enddate><creator>Maciejak, Piotr</creator><creator>Krząścik, Paweł</creator><creator>Członkowska, Agnieszka I.</creator><creator>Szyndler, Janusz</creator><creator>Bidziński, Andrzej</creator><creator>Walkowiak, Jerzy</creator><creator>Kostowski, Wojciech</creator><creator>Plaznik, Adam</creator><general>Elsevier Inc</general><general>Elsevier Science</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>7QG</scope></search><sort><creationdate>20020701</creationdate><title>Antagonism of picrotoxin-induced changes in dopamine and serotonin metabolism by allopregnanolone and midazolam</title><author>Maciejak, Piotr ; Krząścik, Paweł ; Członkowska, Agnieszka I. ; Szyndler, Janusz ; Bidziński, Andrzej ; Walkowiak, Jerzy ; Kostowski, Wojciech ; Plaznik, Adam</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-ca65268945a5bdd2f37de45edd34524acbebbfe2bba82e1f2d147fd2f515c18f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Allopregnanolone</topic><topic>Amino Acids - metabolism</topic><topic>Animals</topic><topic>Anticonvulsants. Antiepileptics. Antiparkinson agents</topic><topic>Biological and medical sciences</topic><topic>Convulsants - pharmacology</topic><topic>Dopamine</topic><topic>Dopamine - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>GABA Antagonists - pharmacology</topic><topic>GABA Modulators - pharmacology</topic><topic>Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy</topic><topic>Injections, Intraventricular</topic><topic>Intracerebroventricular injections</topic><topic>Intraperitoneal injections</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Microinjections</topic><topic>Midazolam</topic><topic>Midazolam - pharmacology</topic><topic>Nervous system (semeiology, syndromes)</topic><topic>Neurology</topic><topic>Neuropharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Picrotoxin</topic><topic>Picrotoxin - antagonists & inhibitors</topic><topic>Picrotoxin - pharmacology</topic><topic>Pregnanolone - pharmacology</topic><topic>Seizures</topic><topic>Seizures - chemically induced</topic><topic>Seizures - psychology</topic><topic>Serotonin</topic><topic>Serotonin - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Maciejak, Piotr</creatorcontrib><creatorcontrib>Krząścik, Paweł</creatorcontrib><creatorcontrib>Członkowska, Agnieszka I.</creatorcontrib><creatorcontrib>Szyndler, Janusz</creatorcontrib><creatorcontrib>Bidziński, Andrzej</creatorcontrib><creatorcontrib>Walkowiak, Jerzy</creatorcontrib><creatorcontrib>Kostowski, Wojciech</creatorcontrib><creatorcontrib>Plaznik, Adam</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>Animal Behavior Abstracts</collection><jtitle>Pharmacology, biochemistry and behavior</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Maciejak, Piotr</au><au>Krząścik, Paweł</au><au>Członkowska, Agnieszka I.</au><au>Szyndler, Janusz</au><au>Bidziński, Andrzej</au><au>Walkowiak, Jerzy</au><au>Kostowski, Wojciech</au><au>Plaznik, Adam</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antagonism of picrotoxin-induced changes in dopamine and serotonin metabolism by allopregnanolone and midazolam</atitle><jtitle>Pharmacology, biochemistry and behavior</jtitle><addtitle>Pharmacol Biochem Behav</addtitle><date>2002-07-01</date><risdate>2002</risdate><volume>72</volume><issue>4</issue><spage>987</spage><epage>991</epage><pages>987-991</pages><issn>0091-3057</issn><eissn>1873-5177</eissn><coden>PBBHAU</coden><abstract>The effects of allopregnanolone and midazolam, given intracerebroventricularly, on the behavioral and biochemical effects of picrotoxin, were examined in a model of neurotoxin-induced seizures, in mice. After acute injections, midazolam (ED
50=39.8 nmol) and allopregnanolone (ED
50=11.0 nmol) produced similar and dose-dependent protection against picrotoxin-induced seizures. Picrotoxin given intraperitoneally at the ED
85 dose decreased significantly the concentration of serotonin (5-HT), dopamine (DA), homovanilic acid (HVA) and 3,4-dihydroxyindolacetic acid (DOPAC), in the mouse striatum and the frontal cortex, in the period of time immediately preceding the onset of seizures. A single injection of allopregnanolone more potently, in comparison to midazolam, antagonized the biochemical action of picrotoxin, abolishing its effects on DA, HVA and 5-HT concentration, in the mouse striatum and the frontal cortex. These results for the first time provide a direct argument for an involvement of central dopaminergic and serotonergic systems in the seizure development. The present data add also to the accumulating evidence suggesting a favorable pharmacological profile for some neurosteroids currently considered to have a future role in the management of epilepsy.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>12062590</pmid><doi>10.1016/S0091-3057(02)00811-0</doi><tpages>5</tpages></addata></record> |
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| subjects | Allopregnanolone Amino Acids - metabolism Animals Anticonvulsants. Antiepileptics. Antiparkinson agents Biological and medical sciences Convulsants - pharmacology Dopamine Dopamine - metabolism Dose-Response Relationship, Drug GABA Antagonists - pharmacology GABA Modulators - pharmacology Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy Injections, Intraventricular Intracerebroventricular injections Intraperitoneal injections Male Medical sciences Mice Microinjections Midazolam Midazolam - pharmacology Nervous system (semeiology, syndromes) Neurology Neuropharmacology Pharmacology. Drug treatments Picrotoxin Picrotoxin - antagonists & inhibitors Picrotoxin - pharmacology Pregnanolone - pharmacology Seizures Seizures - chemically induced Seizures - psychology Serotonin Serotonin - metabolism |
| title | Antagonism of picrotoxin-induced changes in dopamine and serotonin metabolism by allopregnanolone and midazolam |
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