The Potent, Selective mGlu2/3 Receptor Agonist LY379268 Increases Extracellular Levels of Dopamine, 3,4‐Dihydroxyphenylacetic Acid, Homovanillic Acid, and 5‐Hydroxyindole‐3‐Acetic Acid in the Medial Prefrontal Cortex of the Freely Moving Rat
: Previous work has shown that the potent, selective metabotropic glutamate mGlu2/3 receptor agonist LY379268 acts like the atypical antipsychotic clozapine in behavioral assays. To investigate further the potential antipsychotic actions of this agent, we examined the effects of LY379268 using micro...
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creator | Cartmell, Jayne Perry, Kenneth W. Salhoff, Craig R. Monn, James A. Schoepp, Darryle D. |
description | : Previous work has shown that the potent, selective
metabotropic glutamate mGlu2/3 receptor agonist LY379268 acts like the
atypical antipsychotic clozapine in behavioral assays. To investigate further
the potential antipsychotic actions of this agent, we examined the effects of
LY379268 using microdialysis in awake, freely moving rats, on extracellular
levels of dopamine, 3,4‐dihydroxyphenylacetic acid (DOPAC), homovanillic acid
(HVA), and 5‐hydroxyindole‐3‐acetic acid (5‐HIAA) in rat medial prefrontal
cortex. Systemic LY379268 increased extracellular levels of dopamine, DOPAC,
HVA, and 5‐HIAA in a dose‐dependent, somewhat delayed manner. LY379268 (3
mg/kg s.c.) increased levels of dopamine, DOPAC, HVA, and 5‐HIAA to 168, 170,
169, and 151% of basal, respectively. Clozapine (10 mg/kg) also increased
dopamine, DOPAC, and HVA levels, with increases of 255, 262, and 173%,
respectively, but was without effect on extracellular 5‐HIAA levels by 3 mg/kg
LY379268 were reversed by the selective mGlu2/3 receptor antagonist LY341495
(1 mg/kg). Furthermore, LY379268 (3 mg/kg)‐evoked increases in DOPAC and HVA
were partially blocked and the increase in 5‐HIAA was completely blocked by
local application of 3 μM tetrodotoxin. Therefore, we have demonstrated that mGlu2/3 receptor agonists activate dopaminergic and serotonergic brain pathways previously associated with the action of atypical antipsychotics such as clozapine and other psychiatric agents. |
doi_str_mv | 10.1046/j.1471-4159.2000.0751147.x |
format | Article |
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metabotropic glutamate mGlu2/3 receptor agonist LY379268 acts like the
atypical antipsychotic clozapine in behavioral assays. To investigate further
the potential antipsychotic actions of this agent, we examined the effects of
LY379268 using microdialysis in awake, freely moving rats, on extracellular
levels of dopamine, 3,4‐dihydroxyphenylacetic acid (DOPAC), homovanillic acid
(HVA), and 5‐hydroxyindole‐3‐acetic acid (5‐HIAA) in rat medial prefrontal
cortex. Systemic LY379268 increased extracellular levels of dopamine, DOPAC,
HVA, and 5‐HIAA in a dose‐dependent, somewhat delayed manner. LY379268 (3
mg/kg s.c.) increased levels of dopamine, DOPAC, HVA, and 5‐HIAA to 168, 170,
169, and 151% of basal, respectively. Clozapine (10 mg/kg) also increased
dopamine, DOPAC, and HVA levels, with increases of 255, 262, and 173%,
respectively, but was without effect on extracellular 5‐HIAA levels by 3 mg/kg
LY379268 were reversed by the selective mGlu2/3 receptor antagonist LY341495
(1 mg/kg). Furthermore, LY379268 (3 mg/kg)‐evoked increases in DOPAC and HVA
were partially blocked and the increase in 5‐HIAA was completely blocked by
local application of 3 μM tetrodotoxin. Therefore, we have demonstrated that mGlu2/3 receptor agonists activate dopaminergic and serotonergic brain pathways previously associated with the action of atypical antipsychotics such as clozapine and other psychiatric agents.</description><identifier>ISSN: 0022-3042</identifier><identifier>EISSN: 1471-4159</identifier><identifier>DOI: 10.1046/j.1471-4159.2000.0751147.x</identifier><identifier>PMID: 10936197</identifier><identifier>CODEN: JONRA9</identifier><language>eng</language><publisher>Oxford UK: Blackwell Science Ltd</publisher><subject>3,4-Dihydroxyphenylacetic acid ; 3,4-Dihydroxyphenylacetic Acid - metabolism ; 5-Hydroxyindole-3-acetic acid ; Amino Acids - pharmacology ; Animals ; Biological and medical sciences ; Bridged Bicyclo Compounds, Heterocyclic - pharmacology ; Clozapine ; Clozapine - pharmacology ; Dopamine - metabolism ; Excitatory Amino Acid Agonists - pharmacology ; Excitatory Amino Acid Antagonists - pharmacology ; Glutamatergic system (aspartate and other excitatory aminoacids) ; homovanillic acid ; Homovanillic Acid - metabolism ; Hydroxyindoleacetic Acid - metabolism ; Kinetics ; LY379268 ; Male ; Medical sciences ; Metabotropic glutamate receptor ; Microdialysis ; Neuropharmacology ; Neurotransmitters. Neurotransmission. Receptors ; Pharmacology. Drug treatments ; Prefrontal Cortex - drug effects ; Prefrontal Cortex - metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Metabotropic Glutamate - agonists ; Xanthenes - pharmacology</subject><ispartof>Journal of neurochemistry, 2000-09, Vol.75 (3), p.1147-1154</ispartof><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4997-8c28e1e04a330fbc98ed5848f1f72b7ee04a602253525388241ca55275067ac73</citedby><cites>FETCH-LOGICAL-c4997-8c28e1e04a330fbc98ed5848f1f72b7ee04a602253525388241ca55275067ac73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1046%2Fj.1471-4159.2000.0751147.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.1471-4159.2000.0751147.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=801912$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10936197$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cartmell, Jayne</creatorcontrib><creatorcontrib>Perry, Kenneth W.</creatorcontrib><creatorcontrib>Salhoff, Craig R.</creatorcontrib><creatorcontrib>Monn, James A.</creatorcontrib><creatorcontrib>Schoepp, Darryle D.</creatorcontrib><title>The Potent, Selective mGlu2/3 Receptor Agonist LY379268 Increases Extracellular Levels of Dopamine, 3,4‐Dihydroxyphenylacetic Acid, Homovanillic Acid, and 5‐Hydroxyindole‐3‐Acetic Acid in the Medial Prefrontal Cortex of the Freely Moving Rat</title><title>Journal of neurochemistry</title><addtitle>J Neurochem</addtitle><description>: Previous work has shown that the potent, selective
metabotropic glutamate mGlu2/3 receptor agonist LY379268 acts like the
atypical antipsychotic clozapine in behavioral assays. To investigate further
the potential antipsychotic actions of this agent, we examined the effects of
LY379268 using microdialysis in awake, freely moving rats, on extracellular
levels of dopamine, 3,4‐dihydroxyphenylacetic acid (DOPAC), homovanillic acid
(HVA), and 5‐hydroxyindole‐3‐acetic acid (5‐HIAA) in rat medial prefrontal
cortex. Systemic LY379268 increased extracellular levels of dopamine, DOPAC,
HVA, and 5‐HIAA in a dose‐dependent, somewhat delayed manner. LY379268 (3
mg/kg s.c.) increased levels of dopamine, DOPAC, HVA, and 5‐HIAA to 168, 170,
169, and 151% of basal, respectively. Clozapine (10 mg/kg) also increased
dopamine, DOPAC, and HVA levels, with increases of 255, 262, and 173%,
respectively, but was without effect on extracellular 5‐HIAA levels by 3 mg/kg
LY379268 were reversed by the selective mGlu2/3 receptor antagonist LY341495
(1 mg/kg). Furthermore, LY379268 (3 mg/kg)‐evoked increases in DOPAC and HVA
were partially blocked and the increase in 5‐HIAA was completely blocked by
local application of 3 μM tetrodotoxin. Therefore, we have demonstrated that mGlu2/3 receptor agonists activate dopaminergic and serotonergic brain pathways previously associated with the action of atypical antipsychotics such as clozapine and other psychiatric agents.</description><subject>3,4-Dihydroxyphenylacetic acid</subject><subject>3,4-Dihydroxyphenylacetic Acid - metabolism</subject><subject>5-Hydroxyindole-3-acetic acid</subject><subject>Amino Acids - pharmacology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Bridged Bicyclo Compounds, Heterocyclic - pharmacology</subject><subject>Clozapine</subject><subject>Clozapine - pharmacology</subject><subject>Dopamine - metabolism</subject><subject>Excitatory Amino Acid Agonists - pharmacology</subject><subject>Excitatory Amino Acid Antagonists - pharmacology</subject><subject>Glutamatergic system (aspartate and other excitatory aminoacids)</subject><subject>homovanillic acid</subject><subject>Homovanillic Acid - metabolism</subject><subject>Hydroxyindoleacetic Acid - metabolism</subject><subject>Kinetics</subject><subject>LY379268</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metabotropic glutamate receptor</subject><subject>Microdialysis</subject><subject>Neuropharmacology</subject><subject>Neurotransmitters. Neurotransmission. Receptors</subject><subject>Pharmacology. Drug treatments</subject><subject>Prefrontal Cortex - drug effects</subject><subject>Prefrontal Cortex - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Metabotropic Glutamate - agonists</subject><subject>Xanthenes - pharmacology</subject><issn>0022-3042</issn><issn>1471-4159</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVks-O0zAQxiMEYsvCKyALJE5t146dOOFWun-6qAurZTlwilxnsnXl2MV2S3PjEXhG3oIbjloVboiDZXvm99kzoy9JXhE8JpjlZ6sxYZyMGMnKcYoxHmOekRga7x4lg2PqcTLAOE1HFLP0JHnm_QpjkrOcPE1OCC5pTko-SH7dLwHd2gAmDNEn0CCD2gJqr_QmPaPoDiSsg3Vo8mCN8gHNv1BepnmBro10IDx4dLELTkjQeqOFQ3PYgvbINujcrkWrDAwRHbKf33-cq2VXO7vr1kswnY6SoCSaSFUP0cy2diuM0voYEqZGWZTN9iJlaqsh3mlckz9apAwKsYcbqJXQ6NZB46wJ8Ti1LsCur6TPXzoA3aEbu1XmAd2J8Dx50gjt4cVhP00-X17cT2ej-cer6-lkPpKsLPmokGkBBDATlOJmIcsC6qxgRUMani449Jk8zjmjWVxFkTIiRZalPMM5F5LT0-TN_t21s1834EPVKt-PSxiwG19xwmlesuKfIOF5fD1nEXy7B6Wz3seGq7VTrXBdRXDVO6RaVb0Nqt4GVe-Q6uCQahfFLw-_bBYt1H9J95aIwOsDILwUunHCSOWPXIFJSdJIvdtT35SG7j8KqN5_mB4u9DewoNwg</recordid><startdate>200009</startdate><enddate>200009</enddate><creator>Cartmell, Jayne</creator><creator>Perry, Kenneth W.</creator><creator>Salhoff, Craig R.</creator><creator>Monn, James A.</creator><creator>Schoepp, Darryle D.</creator><general>Blackwell Science Ltd</general><general>Blackwell</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><scope>7X8</scope></search><sort><creationdate>200009</creationdate><title>The Potent, Selective mGlu2/3 Receptor Agonist LY379268 Increases Extracellular Levels of Dopamine, 3,4‐Dihydroxyphenylacetic Acid, Homovanillic Acid, and 5‐Hydroxyindole‐3‐Acetic Acid in the Medial Prefrontal Cortex of the Freely Moving Rat</title><author>Cartmell, Jayne ; Perry, Kenneth W. ; Salhoff, Craig R. ; Monn, James A. ; Schoepp, Darryle D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4997-8c28e1e04a330fbc98ed5848f1f72b7ee04a602253525388241ca55275067ac73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>3,4-Dihydroxyphenylacetic acid</topic><topic>3,4-Dihydroxyphenylacetic Acid - metabolism</topic><topic>5-Hydroxyindole-3-acetic acid</topic><topic>Amino Acids - pharmacology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Bridged Bicyclo Compounds, Heterocyclic - pharmacology</topic><topic>Clozapine</topic><topic>Clozapine - pharmacology</topic><topic>Dopamine - metabolism</topic><topic>Excitatory Amino Acid Agonists - pharmacology</topic><topic>Excitatory Amino Acid Antagonists - pharmacology</topic><topic>Glutamatergic system (aspartate and other excitatory aminoacids)</topic><topic>homovanillic acid</topic><topic>Homovanillic Acid - metabolism</topic><topic>Hydroxyindoleacetic Acid - metabolism</topic><topic>Kinetics</topic><topic>LY379268</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metabotropic glutamate receptor</topic><topic>Microdialysis</topic><topic>Neuropharmacology</topic><topic>Neurotransmitters. Neurotransmission. Receptors</topic><topic>Pharmacology. Drug treatments</topic><topic>Prefrontal Cortex - drug effects</topic><topic>Prefrontal Cortex - metabolism</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Metabotropic Glutamate - agonists</topic><topic>Xanthenes - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cartmell, Jayne</creatorcontrib><creatorcontrib>Perry, Kenneth W.</creatorcontrib><creatorcontrib>Salhoff, Craig R.</creatorcontrib><creatorcontrib>Monn, James A.</creatorcontrib><creatorcontrib>Schoepp, Darryle D.</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><collection>MEDLINE - Academic</collection><jtitle>Journal of neurochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cartmell, Jayne</au><au>Perry, Kenneth W.</au><au>Salhoff, Craig R.</au><au>Monn, James A.</au><au>Schoepp, Darryle D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Potent, Selective mGlu2/3 Receptor Agonist LY379268 Increases Extracellular Levels of Dopamine, 3,4‐Dihydroxyphenylacetic Acid, Homovanillic Acid, and 5‐Hydroxyindole‐3‐Acetic Acid in the Medial Prefrontal Cortex of the Freely Moving Rat</atitle><jtitle>Journal of neurochemistry</jtitle><addtitle>J Neurochem</addtitle><date>2000-09</date><risdate>2000</risdate><volume>75</volume><issue>3</issue><spage>1147</spage><epage>1154</epage><pages>1147-1154</pages><issn>0022-3042</issn><eissn>1471-4159</eissn><coden>JONRA9</coden><abstract>: Previous work has shown that the potent, selective
metabotropic glutamate mGlu2/3 receptor agonist LY379268 acts like the
atypical antipsychotic clozapine in behavioral assays. To investigate further
the potential antipsychotic actions of this agent, we examined the effects of
LY379268 using microdialysis in awake, freely moving rats, on extracellular
levels of dopamine, 3,4‐dihydroxyphenylacetic acid (DOPAC), homovanillic acid
(HVA), and 5‐hydroxyindole‐3‐acetic acid (5‐HIAA) in rat medial prefrontal
cortex. Systemic LY379268 increased extracellular levels of dopamine, DOPAC,
HVA, and 5‐HIAA in a dose‐dependent, somewhat delayed manner. LY379268 (3
mg/kg s.c.) increased levels of dopamine, DOPAC, HVA, and 5‐HIAA to 168, 170,
169, and 151% of basal, respectively. Clozapine (10 mg/kg) also increased
dopamine, DOPAC, and HVA levels, with increases of 255, 262, and 173%,
respectively, but was without effect on extracellular 5‐HIAA levels by 3 mg/kg
LY379268 were reversed by the selective mGlu2/3 receptor antagonist LY341495
(1 mg/kg). Furthermore, LY379268 (3 mg/kg)‐evoked increases in DOPAC and HVA
were partially blocked and the increase in 5‐HIAA was completely blocked by
local application of 3 μM tetrodotoxin. Therefore, we have demonstrated that mGlu2/3 receptor agonists activate dopaminergic and serotonergic brain pathways previously associated with the action of atypical antipsychotics such as clozapine and other psychiatric agents.</abstract><cop>Oxford UK</cop><pub>Blackwell Science Ltd</pub><pmid>10936197</pmid><doi>10.1046/j.1471-4159.2000.0751147.x</doi><tpages>8</tpages></addata></record> |
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source | MEDLINE; Access via Wiley Online Library; IngentaConnect Open Access Journals; EZB-FREE-00999 freely available EZB journals; Wiley Online Library (Open Access Collection); Free Full-Text Journals in Chemistry |
subjects | 3,4-Dihydroxyphenylacetic acid 3,4-Dihydroxyphenylacetic Acid - metabolism 5-Hydroxyindole-3-acetic acid Amino Acids - pharmacology Animals Biological and medical sciences Bridged Bicyclo Compounds, Heterocyclic - pharmacology Clozapine Clozapine - pharmacology Dopamine - metabolism Excitatory Amino Acid Agonists - pharmacology Excitatory Amino Acid Antagonists - pharmacology Glutamatergic system (aspartate and other excitatory aminoacids) homovanillic acid Homovanillic Acid - metabolism Hydroxyindoleacetic Acid - metabolism Kinetics LY379268 Male Medical sciences Metabotropic glutamate receptor Microdialysis Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Pharmacology. Drug treatments Prefrontal Cortex - drug effects Prefrontal Cortex - metabolism Rats Rats, Sprague-Dawley Receptors, Metabotropic Glutamate - agonists Xanthenes - pharmacology |
title | The Potent, Selective mGlu2/3 Receptor Agonist LY379268 Increases Extracellular Levels of Dopamine, 3,4‐Dihydroxyphenylacetic Acid, Homovanillic Acid, and 5‐Hydroxyindole‐3‐Acetic Acid in the Medial Prefrontal Cortex of the Freely Moving Rat |
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