Mechanisms underlying the antidopaminergic effect of clonazepam and melatonin in striatum
Intrastriatal injection of the GABA A antagonist, bicuculline, caused about a 75% decrease in the inhibitory effect of the central-type benzodiazepine (BZ) agonist, clonazepam or the indoleamine hormone, melatonin, on apomorphine-induced rotation in a 6-hydroxydopamine model of dopaminergic supersen...
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| Veröffentlicht in: | Neuropharmacology 1997-11, Vol.36 (11), p.1659-1663 |
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| creator | Tenn, C.C. Niles, L.P. |
| description | Intrastriatal injection of the GABA
A antagonist, bicuculline, caused about a 75% decrease in the inhibitory effect of the central-type benzodiazepine (BZ) agonist, clonazepam or the indoleamine hormone, melatonin, on apomorphine-induced rotation in a 6-hydroxydopamine model of dopaminergic supersensitivity. Pretreatment with the peripheral-type BZ antagonist, PK 11195 (intrastriatally or intraperitoneally), also attenuated the antidopaminergic effect of these drugs but with much less potency than bicuculline. However, the combination of both bicuculline and PK 11195, injected directly into the striatum, completely blocked the antidopaminergic action of clonazepam or melatonin. These results indicate that the antidopaminergic action of clonazepam and melatonin in the striatum involves two distinct mechanisms: (1) a predominant GABAergic activation via the BZ/GABA
A receptor complex, and (2) a secondary mechanism linked to a PK 11195- sensitive BZ receptor pathway. Recent studies indicate that PK 11195 blocks BZ-induced inhibition of the adenylyl cyclase-cyclic AMP pathway in the striatum. Since cyclic AMP has been implicated in the rotational behaviour of 6-hydroxydopamine-lesioned animals, it is possible that the antidopaminergic action of clonazepam and melatonin also involves suppression of this second messenger. All rights reserved. |
| doi_str_mv | 10.1016/S0028-3908(97)00165-2 |
| format | Article |
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A antagonist, bicuculline, caused about a 75% decrease in the inhibitory effect of the central-type benzodiazepine (BZ) agonist, clonazepam or the indoleamine hormone, melatonin, on apomorphine-induced rotation in a 6-hydroxydopamine model of dopaminergic supersensitivity. Pretreatment with the peripheral-type BZ antagonist, PK 11195 (intrastriatally or intraperitoneally), also attenuated the antidopaminergic effect of these drugs but with much less potency than bicuculline. However, the combination of both bicuculline and PK 11195, injected directly into the striatum, completely blocked the antidopaminergic action of clonazepam or melatonin. These results indicate that the antidopaminergic action of clonazepam and melatonin in the striatum involves two distinct mechanisms: (1) a predominant GABAergic activation via the BZ/GABA
A receptor complex, and (2) a secondary mechanism linked to a PK 11195- sensitive BZ receptor pathway. Recent studies indicate that PK 11195 blocks BZ-induced inhibition of the adenylyl cyclase-cyclic AMP pathway in the striatum. Since cyclic AMP has been implicated in the rotational behaviour of 6-hydroxydopamine-lesioned animals, it is possible that the antidopaminergic action of clonazepam and melatonin also involves suppression of this second messenger. All rights reserved.</description><identifier>ISSN: 0028-3908</identifier><identifier>EISSN: 1873-7064</identifier><identifier>DOI: 10.1016/S0028-3908(97)00165-2</identifier><identifier>PMID: 9517437</identifier><identifier>CODEN: NEPHBW</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject><![CDATA[6-hydroxydopamine lesioning ; Animals ; Benzodiazepine receptor ; bicuculline ; Bicuculline - administration & dosage ; Bicuculline - pharmacology ; Biological and medical sciences ; Clonazepam - administration & dosage ; Clonazepam - pharmacology ; cyclic AMP ; Dopamine Antagonists - administration & dosage ; Dopamine Antagonists - pharmacology ; dopaminergic supersensitivity ; Dose-Response Relationship, Drug ; GABA Antagonists - administration & dosage ; GABA Antagonists - pharmacology ; GABA Modulators - administration & dosage ; GABA Modulators - pharmacology ; Injections, Intraperitoneal ; intrastriatal injection ; Isoquinolines - administration & dosage ; Isoquinolines - pharmacology ; Male ; Medical sciences ; Melatonin - administration & dosage ; Melatonin - pharmacology ; Microinjections ; Neostriatum - drug effects ; Neostriatum - physiology ; Neuropharmacology ; Oxidopamine - toxicity ; Pharmacology. Drug treatments ; PK 11195 ; Psycholeptics: tranquillizer, neuroleptic ; Psychology. Psychoanalysis. Psychiatry ; Psychopharmacology ; Rats ; Rats, Sprague-Dawley ; Sympatholytics - toxicity]]></subject><ispartof>Neuropharmacology, 1997-11, Vol.36 (11), p.1659-1663</ispartof><rights>1998</rights><rights>1998 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c420t-976f7db85fa59179168440f2960f79e3b003d9d1c90f939ad4b7d58819308b483</citedby><cites>FETCH-LOGICAL-c420t-976f7db85fa59179168440f2960f79e3b003d9d1c90f939ad4b7d58819308b483</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0028390897001652$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2149693$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9517437$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tenn, C.C.</creatorcontrib><creatorcontrib>Niles, L.P.</creatorcontrib><title>Mechanisms underlying the antidopaminergic effect of clonazepam and melatonin in striatum</title><title>Neuropharmacology</title><addtitle>Neuropharmacology</addtitle><description>Intrastriatal injection of the GABA
A antagonist, bicuculline, caused about a 75% decrease in the inhibitory effect of the central-type benzodiazepine (BZ) agonist, clonazepam or the indoleamine hormone, melatonin, on apomorphine-induced rotation in a 6-hydroxydopamine model of dopaminergic supersensitivity. Pretreatment with the peripheral-type BZ antagonist, PK 11195 (intrastriatally or intraperitoneally), also attenuated the antidopaminergic effect of these drugs but with much less potency than bicuculline. However, the combination of both bicuculline and PK 11195, injected directly into the striatum, completely blocked the antidopaminergic action of clonazepam or melatonin. These results indicate that the antidopaminergic action of clonazepam and melatonin in the striatum involves two distinct mechanisms: (1) a predominant GABAergic activation via the BZ/GABA
A receptor complex, and (2) a secondary mechanism linked to a PK 11195- sensitive BZ receptor pathway. Recent studies indicate that PK 11195 blocks BZ-induced inhibition of the adenylyl cyclase-cyclic AMP pathway in the striatum. Since cyclic AMP has been implicated in the rotational behaviour of 6-hydroxydopamine-lesioned animals, it is possible that the antidopaminergic action of clonazepam and melatonin also involves suppression of this second messenger. All rights reserved.</description><subject>6-hydroxydopamine lesioning</subject><subject>Animals</subject><subject>Benzodiazepine receptor</subject><subject>bicuculline</subject><subject>Bicuculline - administration & dosage</subject><subject>Bicuculline - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Clonazepam - administration & dosage</subject><subject>Clonazepam - pharmacology</subject><subject>cyclic AMP</subject><subject>Dopamine Antagonists - administration & dosage</subject><subject>Dopamine Antagonists - pharmacology</subject><subject>dopaminergic supersensitivity</subject><subject>Dose-Response Relationship, Drug</subject><subject>GABA Antagonists - administration & dosage</subject><subject>GABA Antagonists - pharmacology</subject><subject>GABA Modulators - administration & dosage</subject><subject>GABA Modulators - pharmacology</subject><subject>Injections, Intraperitoneal</subject><subject>intrastriatal injection</subject><subject>Isoquinolines - administration & dosage</subject><subject>Isoquinolines - pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Melatonin - administration & dosage</subject><subject>Melatonin - pharmacology</subject><subject>Microinjections</subject><subject>Neostriatum - drug effects</subject><subject>Neostriatum - physiology</subject><subject>Neuropharmacology</subject><subject>Oxidopamine - toxicity</subject><subject>Pharmacology. Drug treatments</subject><subject>PK 11195</subject><subject>Psycholeptics: tranquillizer, neuroleptic</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Sympatholytics - toxicity</subject><issn>0028-3908</issn><issn>1873-7064</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEFLHTEQx0NpsU_tRxD2IEUPayeb7CY5SRG1gsVD66GnkE0mGtnNPpPdgn76Rt_jXQsDA_P_zST8CDmicEaBdt9-ATSyZgrkiRKnUEZt3XwgKyoFqwV0_CNZ7ZDPZD_nJwDgkso9sqdaKjgTK_LnJ9pHE0Mec7VEh2l4CfGhmh-xMnEOblqbMURMD8FW6D3auZp8ZYcpmlcsWaFcNeJg5imGWJXKcwpmXsZD8smbIeOXbT8g91eXvy9-1Ld31zcX329ryxuYayU6L1wvW29aRYWineQcfKM68EIh6wGYU45aBV4xZRzvhWulpIqB7LlkB-Tr5u46Tc8L5lmPIVscBhNxWrIuXjhQLgrYbkCbppwTer1OYTTpRVPQb0r1u1L95ksrod-V6qbsHW0fWPoR3W5r67Dkx9vcZGsGn0y0Ie-whnLVKVaw8w2GRcbfgElnGzBadCEVrdpN4T8f-QcwWJLE</recordid><startdate>19971101</startdate><enddate>19971101</enddate><creator>Tenn, C.C.</creator><creator>Niles, L.P.</creator><general>Elsevier Ltd</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>19971101</creationdate><title>Mechanisms underlying the antidopaminergic effect of clonazepam and melatonin in striatum</title><author>Tenn, C.C. ; Niles, L.P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c420t-976f7db85fa59179168440f2960f79e3b003d9d1c90f939ad4b7d58819308b483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>6-hydroxydopamine lesioning</topic><topic>Animals</topic><topic>Benzodiazepine receptor</topic><topic>bicuculline</topic><topic>Bicuculline - administration & dosage</topic><topic>Bicuculline - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Clonazepam - administration & dosage</topic><topic>Clonazepam - pharmacology</topic><topic>cyclic AMP</topic><topic>Dopamine Antagonists - administration & dosage</topic><topic>Dopamine Antagonists - pharmacology</topic><topic>dopaminergic supersensitivity</topic><topic>Dose-Response Relationship, Drug</topic><topic>GABA Antagonists - administration & dosage</topic><topic>GABA Antagonists - pharmacology</topic><topic>GABA Modulators - administration & dosage</topic><topic>GABA Modulators - pharmacology</topic><topic>Injections, Intraperitoneal</topic><topic>intrastriatal injection</topic><topic>Isoquinolines - administration & dosage</topic><topic>Isoquinolines - pharmacology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Melatonin - administration & dosage</topic><topic>Melatonin - pharmacology</topic><topic>Microinjections</topic><topic>Neostriatum - drug effects</topic><topic>Neostriatum - physiology</topic><topic>Neuropharmacology</topic><topic>Oxidopamine - toxicity</topic><topic>Pharmacology. Drug treatments</topic><topic>PK 11195</topic><topic>Psycholeptics: tranquillizer, neuroleptic</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Sympatholytics - toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tenn, C.C.</creatorcontrib><creatorcontrib>Niles, L.P.</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>Neuropharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tenn, C.C.</au><au>Niles, L.P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mechanisms underlying the antidopaminergic effect of clonazepam and melatonin in striatum</atitle><jtitle>Neuropharmacology</jtitle><addtitle>Neuropharmacology</addtitle><date>1997-11-01</date><risdate>1997</risdate><volume>36</volume><issue>11</issue><spage>1659</spage><epage>1663</epage><pages>1659-1663</pages><issn>0028-3908</issn><eissn>1873-7064</eissn><coden>NEPHBW</coden><abstract>Intrastriatal injection of the GABA
A antagonist, bicuculline, caused about a 75% decrease in the inhibitory effect of the central-type benzodiazepine (BZ) agonist, clonazepam or the indoleamine hormone, melatonin, on apomorphine-induced rotation in a 6-hydroxydopamine model of dopaminergic supersensitivity. Pretreatment with the peripheral-type BZ antagonist, PK 11195 (intrastriatally or intraperitoneally), also attenuated the antidopaminergic effect of these drugs but with much less potency than bicuculline. However, the combination of both bicuculline and PK 11195, injected directly into the striatum, completely blocked the antidopaminergic action of clonazepam or melatonin. These results indicate that the antidopaminergic action of clonazepam and melatonin in the striatum involves two distinct mechanisms: (1) a predominant GABAergic activation via the BZ/GABA
A receptor complex, and (2) a secondary mechanism linked to a PK 11195- sensitive BZ receptor pathway. Recent studies indicate that PK 11195 blocks BZ-induced inhibition of the adenylyl cyclase-cyclic AMP pathway in the striatum. Since cyclic AMP has been implicated in the rotational behaviour of 6-hydroxydopamine-lesioned animals, it is possible that the antidopaminergic action of clonazepam and melatonin also involves suppression of this second messenger. All rights reserved.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>9517437</pmid><doi>10.1016/S0028-3908(97)00165-2</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-3908 |
| ispartof | Neuropharmacology, 1997-11, Vol.36 (11), p.1659-1663 |
| issn | 0028-3908 1873-7064 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | 6-hydroxydopamine lesioning Animals Benzodiazepine receptor bicuculline Bicuculline - administration & dosage Bicuculline - pharmacology Biological and medical sciences Clonazepam - administration & dosage Clonazepam - pharmacology cyclic AMP Dopamine Antagonists - administration & dosage Dopamine Antagonists - pharmacology dopaminergic supersensitivity Dose-Response Relationship, Drug GABA Antagonists - administration & dosage GABA Antagonists - pharmacology GABA Modulators - administration & dosage GABA Modulators - pharmacology Injections, Intraperitoneal intrastriatal injection Isoquinolines - administration & dosage Isoquinolines - pharmacology Male Medical sciences Melatonin - administration & dosage Melatonin - pharmacology Microinjections Neostriatum - drug effects Neostriatum - physiology Neuropharmacology Oxidopamine - toxicity Pharmacology. Drug treatments PK 11195 Psycholeptics: tranquillizer, neuroleptic Psychology. Psychoanalysis. Psychiatry Psychopharmacology Rats Rats, Sprague-Dawley Sympatholytics - toxicity |
| title | Mechanisms underlying the antidopaminergic effect of clonazepam and melatonin in striatum |
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