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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-9-12
pubmed:abstractText
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 microM 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/3,4-Dihydroxyphenylacetic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Amino Acids, http://linkedlifedata.com/resource/pubmed/chemical/Bicyclo Compounds, Heterocyclic, http://linkedlifedata.com/resource/pubmed/chemical/Clozapine, http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Agonists, http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Antagonists, http://linkedlifedata.com/resource/pubmed/chemical/Homovanillic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Hydroxyindoleacetic Acid, http://linkedlifedata.com/resource/pubmed/chemical/LY 341495, http://linkedlifedata.com/resource/pubmed/chemical/LY 379268, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Metabotropic Glutamate, http://linkedlifedata.com/resource/pubmed/chemical/Xanthenes
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
75
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1147-54
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed-meshheading:10936197-3,4-Dihydroxyphenylacetic Acid, pubmed-meshheading:10936197-Amino Acids, pubmed-meshheading:10936197-Animals, pubmed-meshheading:10936197-Bicyclo Compounds, Heterocyclic, pubmed-meshheading:10936197-Clozapine, pubmed-meshheading:10936197-Dopamine, pubmed-meshheading:10936197-Excitatory Amino Acid Agonists, pubmed-meshheading:10936197-Excitatory Amino Acid Antagonists, pubmed-meshheading:10936197-Homovanillic Acid, pubmed-meshheading:10936197-Hydroxyindoleacetic Acid, pubmed-meshheading:10936197-Kinetics, pubmed-meshheading:10936197-Male, pubmed-meshheading:10936197-Prefrontal Cortex, pubmed-meshheading:10936197-Rats, pubmed-meshheading:10936197-Rats, Sprague-Dawley, pubmed-meshheading:10936197-Receptors, Metabotropic Glutamate, pubmed-meshheading:10936197-Xanthenes
pubmed:year
2000
pubmed:articleTitle
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.
pubmed:affiliation
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
pubmed:publicationType
Journal Article