The hallucinogen 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) increases cortical extracellular glutamate levels in rats
Activation of the cerebral cortex is seen during hallucinations. The 5-HT 2A/C agonist 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) is a potent hallucinogen that has been proposed to act by targeting 5-HT 2A heteroceptors on thalamocortical neurons and eliciting release of glutamate from thes...
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| Veröffentlicht in: | Neuroscience letters 2003-08, Vol.346 (3), p.137-140 |
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| container_title | Neuroscience letters |
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| creator | Scruggs, Jennifer L. Schmidt, Dennis Deutch, Ariel Y. |
| description | Activation of the cerebral cortex is seen during hallucinations. The 5-HT
2A/C agonist 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) is a potent hallucinogen that has been proposed to act by targeting 5-HT
2A heteroceptors on thalamocortical neurons and eliciting release of glutamate from these cells, which in turn drives cortical neurons. We used in vivo microdialysis to determine if DOI increases extracellular glutamate levels. Systemic administration of DOI significantly increased extracellular glutamate levels in the somatosensory cortex of the freely-moving rat. Similarly, intracortical administration of DOI by reverse dialysis increased cortical extracellular glutamate levels. No consistent changes in either extracellular GABA or glycine levels were observed in response to DOI. The increase in glutamate levels elicited by intracortical DOI was blocked by treatment with the selective 5-HT
2A antagonist MDL 100,907. These data are consistent with the hypothesis that 5-HT
2A receptor-mediated regulation of glutamate release is the mechanism through which hallucinogens activate the cerebral cortex. |
| doi_str_mv | 10.1016/S0304-3940(03)00547-0 |
| format | Article |
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2A heteroceptors on thalamocortical neurons and eliciting release of glutamate from these cells, which in turn drives cortical neurons. We used in vivo microdialysis to determine if DOI increases extracellular glutamate levels. Systemic administration of DOI significantly increased extracellular glutamate levels in the somatosensory cortex of the freely-moving rat. Similarly, intracortical administration of DOI by reverse dialysis increased cortical extracellular glutamate levels. No consistent changes in either extracellular GABA or glycine levels were observed in response to DOI. The increase in glutamate levels elicited by intracortical DOI was blocked by treatment with the selective 5-HT
2A antagonist MDL 100,907. These data are consistent with the hypothesis that 5-HT
2A receptor-mediated regulation of glutamate release is the mechanism through which hallucinogens activate the cerebral cortex.</description><identifier>ISSN: 0304-3940</identifier><identifier>EISSN: 1872-7972</identifier><identifier>DOI: 10.1016/S0304-3940(03)00547-0</identifier><identifier>PMID: 12853103</identifier><identifier>CODEN: NELED5</identifier><language>eng</language><publisher>Shannon: Elsevier Ireland Ltd</publisher><subject>5-HT 2A receptor ; Amphetamines - administration & dosage ; Amphetamines - pharmacology ; Animals ; Biological and medical sciences ; Cortex ; Extracellular Space - metabolism ; Fluorobenzenes - pharmacology ; Glutamate ; Glutamic Acid - metabolism ; Hallucinogen ; Hallucinogens - administration & dosage ; Hallucinogens - pharmacology ; In vivo microdialysis ; Medical sciences ; Microdialysis ; Neuropharmacology ; Neurotransmitters. Neurotransmission. Receptors ; Pharmacology. Drug treatments ; Piperidines - pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptor, Serotonin, 5-HT2A ; Receptor, Serotonin, 5-HT2C ; Receptors, Serotonin - drug effects ; Serotonin Antagonists - pharmacology ; Serotonin Receptor Agonists - administration & dosage ; Serotonin Receptor Agonists - pharmacology ; Serotoninergic system ; Somatosensory Cortex - drug effects ; Somatosensory Cortex - metabolism ; Thalamus</subject><ispartof>Neuroscience letters, 2003-08, Vol.346 (3), p.137-140</ispartof><rights>2003 Elsevier Science Ireland Ltd</rights><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-d559b50c72f7859d8b5dc3d37f3c616a35674cdc8232970bba36cae95b2982fc3</citedby><cites>FETCH-LOGICAL-c474t-d559b50c72f7859d8b5dc3d37f3c616a35674cdc8232970bba36cae95b2982fc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0304-3940(03)00547-0$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14926096$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12853103$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Scruggs, Jennifer L.</creatorcontrib><creatorcontrib>Schmidt, Dennis</creatorcontrib><creatorcontrib>Deutch, Ariel Y.</creatorcontrib><title>The hallucinogen 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) increases cortical extracellular glutamate levels in rats</title><title>Neuroscience letters</title><addtitle>Neurosci Lett</addtitle><description>Activation of the cerebral cortex is seen during hallucinations. The 5-HT
2A/C agonist 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) is a potent hallucinogen that has been proposed to act by targeting 5-HT
2A heteroceptors on thalamocortical neurons and eliciting release of glutamate from these cells, which in turn drives cortical neurons. We used in vivo microdialysis to determine if DOI increases extracellular glutamate levels. Systemic administration of DOI significantly increased extracellular glutamate levels in the somatosensory cortex of the freely-moving rat. Similarly, intracortical administration of DOI by reverse dialysis increased cortical extracellular glutamate levels. No consistent changes in either extracellular GABA or glycine levels were observed in response to DOI. The increase in glutamate levels elicited by intracortical DOI was blocked by treatment with the selective 5-HT
2A antagonist MDL 100,907. These data are consistent with the hypothesis that 5-HT
2A receptor-mediated regulation of glutamate release is the mechanism through which hallucinogens activate the cerebral cortex.</description><subject>5-HT 2A receptor</subject><subject>Amphetamines - administration & dosage</subject><subject>Amphetamines - pharmacology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cortex</subject><subject>Extracellular Space - metabolism</subject><subject>Fluorobenzenes - pharmacology</subject><subject>Glutamate</subject><subject>Glutamic Acid - metabolism</subject><subject>Hallucinogen</subject><subject>Hallucinogens - administration & dosage</subject><subject>Hallucinogens - pharmacology</subject><subject>In vivo microdialysis</subject><subject>Medical sciences</subject><subject>Microdialysis</subject><subject>Neuropharmacology</subject><subject>Neurotransmitters. Neurotransmission. Receptors</subject><subject>Pharmacology. Drug treatments</subject><subject>Piperidines - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptor, Serotonin, 5-HT2A</subject><subject>Receptor, Serotonin, 5-HT2C</subject><subject>Receptors, Serotonin - drug effects</subject><subject>Serotonin Antagonists - pharmacology</subject><subject>Serotonin Receptor Agonists - administration & dosage</subject><subject>Serotonin Receptor Agonists - pharmacology</subject><subject>Serotoninergic system</subject><subject>Somatosensory Cortex - drug effects</subject><subject>Somatosensory Cortex - metabolism</subject><subject>Thalamus</subject><issn>0304-3940</issn><issn>1872-7972</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0UtrVDEUB_Agih2rH0HJRmnBaJ43NyuR-ioUurCuREJucm4nch9jkls6Gz-7mc5gl11l8zuPnD9CLxl9xyhr3n-ngkoijKQnVJxSqqQm9BFasVZzoo3mj9HqPzlCz3L-TatiSj5FR4y3SjAqVujv1Rrw2g3D4uM0X8OEGfnJ3yoS4ghlPd9uiSRxDvNmDdN2-EU4cWOVmzRv3AT45NPl-SmOk0_gMmTs51SidwOG25Kch9p4cAlfD0txoyuAB7iBIdcKnFzJz9GT3g0ZXhzeY_Tjy-ers2_k4vLr-dnHC-KlloUEpUynqNe8160yoe1U8CII3QvfsMYJ1Wjpg2-54EbTrnOi8Q6M6rhpee_FMXqz71v3_rNALnaMebdd_cO8ZKuFbBrN6YOQtW0rjVYVqj30ac45QW83KY4ubS2jdpeQvUvI7s5vqbB3CdndgFeHAUs3QrivOkRSwesDcLkesk9u8jHfO2l4Q01T3Ye9q-eEmwjJZh9h8hBiAl9smOMDq_wDNdWtfg</recordid><startdate>20030807</startdate><enddate>20030807</enddate><creator>Scruggs, Jennifer L.</creator><creator>Schmidt, Dennis</creator><creator>Deutch, Ariel Y.</creator><general>Elsevier Ireland 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>7U7</scope><scope>C1K</scope><scope>7X8</scope></search><sort><creationdate>20030807</creationdate><title>The hallucinogen 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) increases cortical extracellular glutamate levels in rats</title><author>Scruggs, Jennifer L. ; Schmidt, Dennis ; Deutch, Ariel Y.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-d559b50c72f7859d8b5dc3d37f3c616a35674cdc8232970bba36cae95b2982fc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>5-HT 2A receptor</topic><topic>Amphetamines - administration & dosage</topic><topic>Amphetamines - pharmacology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cortex</topic><topic>Extracellular Space - metabolism</topic><topic>Fluorobenzenes - pharmacology</topic><topic>Glutamate</topic><topic>Glutamic Acid - metabolism</topic><topic>Hallucinogen</topic><topic>Hallucinogens - administration & dosage</topic><topic>Hallucinogens - pharmacology</topic><topic>In vivo microdialysis</topic><topic>Medical sciences</topic><topic>Microdialysis</topic><topic>Neuropharmacology</topic><topic>Neurotransmitters. Neurotransmission. Receptors</topic><topic>Pharmacology. Drug treatments</topic><topic>Piperidines - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptor, Serotonin, 5-HT2A</topic><topic>Receptor, Serotonin, 5-HT2C</topic><topic>Receptors, Serotonin - drug effects</topic><topic>Serotonin Antagonists - pharmacology</topic><topic>Serotonin Receptor Agonists - administration & dosage</topic><topic>Serotonin Receptor Agonists - pharmacology</topic><topic>Serotoninergic system</topic><topic>Somatosensory Cortex - drug effects</topic><topic>Somatosensory Cortex - metabolism</topic><topic>Thalamus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Scruggs, Jennifer L.</creatorcontrib><creatorcontrib>Schmidt, Dennis</creatorcontrib><creatorcontrib>Deutch, Ariel Y.</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>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><jtitle>Neuroscience letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Scruggs, Jennifer L.</au><au>Schmidt, Dennis</au><au>Deutch, Ariel Y.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The hallucinogen 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) increases cortical extracellular glutamate levels in rats</atitle><jtitle>Neuroscience letters</jtitle><addtitle>Neurosci Lett</addtitle><date>2003-08-07</date><risdate>2003</risdate><volume>346</volume><issue>3</issue><spage>137</spage><epage>140</epage><pages>137-140</pages><issn>0304-3940</issn><eissn>1872-7972</eissn><coden>NELED5</coden><abstract>Activation of the cerebral cortex is seen during hallucinations. The 5-HT
2A/C agonist 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) is a potent hallucinogen that has been proposed to act by targeting 5-HT
2A heteroceptors on thalamocortical neurons and eliciting release of glutamate from these cells, which in turn drives cortical neurons. We used in vivo microdialysis to determine if DOI increases extracellular glutamate levels. Systemic administration of DOI significantly increased extracellular glutamate levels in the somatosensory cortex of the freely-moving rat. Similarly, intracortical administration of DOI by reverse dialysis increased cortical extracellular glutamate levels. No consistent changes in either extracellular GABA or glycine levels were observed in response to DOI. The increase in glutamate levels elicited by intracortical DOI was blocked by treatment with the selective 5-HT
2A antagonist MDL 100,907. These data are consistent with the hypothesis that 5-HT
2A receptor-mediated regulation of glutamate release is the mechanism through which hallucinogens activate the cerebral cortex.</abstract><cop>Shannon</cop><pub>Elsevier Ireland Ltd</pub><pmid>12853103</pmid><doi>10.1016/S0304-3940(03)00547-0</doi><tpages>4</tpages></addata></record> |
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| ispartof | Neuroscience letters, 2003-08, Vol.346 (3), p.137-140 |
| issn | 0304-3940 1872-7972 |
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| subjects | 5-HT 2A receptor Amphetamines - administration & dosage Amphetamines - pharmacology Animals Biological and medical sciences Cortex Extracellular Space - metabolism Fluorobenzenes - pharmacology Glutamate Glutamic Acid - metabolism Hallucinogen Hallucinogens - administration & dosage Hallucinogens - pharmacology In vivo microdialysis Medical sciences Microdialysis Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Pharmacology. Drug treatments Piperidines - pharmacology Rats Rats, Sprague-Dawley Receptor, Serotonin, 5-HT2A Receptor, Serotonin, 5-HT2C Receptors, Serotonin - drug effects Serotonin Antagonists - pharmacology Serotonin Receptor Agonists - administration & dosage Serotonin Receptor Agonists - pharmacology Serotoninergic system Somatosensory Cortex - drug effects Somatosensory Cortex - metabolism Thalamus |
| title | The hallucinogen 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) increases cortical extracellular glutamate levels in rats |
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