| gamma-Hydroxybutyrate modulation of glutamate levels in the hippocampus: an in vivo and in vitro study. | |
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MedLine Citation:
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PMID: 11553667 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The effect of gamma-hydroxybutyric acid on extracellular glutamate levels in the hippocampus was studied by microdialysis in freely moving rats and in isolated hippocampal synaptosomes. Intra-hippocampal (CA1) perfusion with gamma-hydroxybutyric acid (10 nM-1 mM) concentration-dependently influenced glutamate levels: gamma-hydroxybutyric acid (100 and 500 nM) increased glutamate levels; 100 and 300 microM concentrations were ineffective; whereas the highest 1 mM concentration reduced local glutamate levels. The stimulant effect of gamma-hydroxybutyric acid (100 nM) was suppressed by the locally co-perfused gamma-hydroxybutyric acid receptor antagonist NCS-382 (10 microM) but not by the GABA(B) receptor antagonist CGP-35348 (500 microM). Furthermore, the gamma-hydroxybutyric acid (1 mM)-induced reduction in CA1 glutamate levels was counteracted by NCS-382 (10 microM), and it was also reversed into an increase by CGP-35348. Given alone, neither NCS-382 nor CGP-35348 modified glutamate levels. In hippocampal synaptosomes, gamma-hydroxybutyric acid (50 and 100 nM) enhanced both the spontaneous and K(+)-evoked glutamate efflux, respectively, both effects being counteracted by NCS-382 (100 nM), but not by CGP-35348 (100 microM). These findings indicate that gamma-hydroxybutyric acid exerts a concentration-dependent regulation of hippocampal glutamate transmission via two opposing mechanisms, whereby a direct gamma-hydroxybutyric acid receptor mediated facilitation is observed at nanomolar gamma-hydroxybutyric acid concentrations, and an indirect GABA(B) receptor mediated inhibition predominates at millimolar concentrations. |
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Authors:
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L Ferraro; S Tanganelli; W T O'Connor; W Francesconi; A Loche; G L Gessa; T Antonelli |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of neurochemistry Volume: 78 ISSN: 0022-3042 ISO Abbreviation: J. Neurochem. Publication Date: 2001 Sep |
Date Detail:
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Created Date: 2001-09-12 Completed Date: 2001-10-25 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2985190R Medline TA: J Neurochem Country: United States |
Other Details:
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Languages: eng Pagination: 929-39 Citation Subset: IM |
Affiliation:
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Department of Clinical and Experimental Medicine, Pharmacology Section, University of Ferrara, Ferrara, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Anesthetics, Intravenous
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pharmacology* Animals Anticonvulsants / pharmacology Benzocycloheptenes / pharmacology Calcium / pharmacology Consciousness / physiology Extracellular Space / metabolism GABA Antagonists / pharmacology Glutamic Acid / metabolism* Hippocampus / drug effects*, metabolism* Male Microdialysis Organophosphorus Compounds / pharmacology Potassium / pharmacology Rats Rats, Sprague-Dawley Sodium Oxybate / pharmacology* Synaptic Transmission / drug effects, physiology Synaptosomes / drug effects, metabolism Tetrodotoxin / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Anesthetics, Intravenous; 0/Anticonvulsants; 0/Benzocycloheptenes; 0/GABA Antagonists; 0/Organophosphorus Compounds; 123690-79-9/CGP 35348; 131733-92-1/NCS 382; 4368-28-9/Tetrodotoxin; 502-85-2/Sodium Oxybate; 56-86-0/Glutamic Acid; 7440-09-7/Potassium; 7440-70-2/Calcium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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