| Decreased 3H-L-quinuclidinyl benzilate binding and muscarine receptor subsensitivity after chronic gamma-butyrolactone treatment. | |
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MedLine Citation:
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PMID: 7329448 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A significant decrease in the number of 3H-quinuclidinyl benzilate (3H-QNB) binding sites in striatal membranes was observed in rats exposed to gamma-butyrolactone (GBL) during 3 weeks. This decrease in 3H-QNB binding was not due to a direct effect of GBL on muscarine receptors since no alterations of binding were produced by high concentrations of GBL or of its active metabolite gammahydroxybutyric acid (GHB) when added in vitro. Challenge doses of pilocarpine were less effective in producing catalepsy and tremors in rats chronically treated with GBL. It is proposed that the partial inhibition of the nigro-striatal dopaminergic pathway produced by chronic GBL treatment leads to a persistent activation of the intrastriatal cholinergic interneurons, which are tonically inhibited by dopaminergic nigrostriatal neurons. The activation of striatal cholinergic interneurons results in a decreased number of muscarine receptors and in a lower sensitivity to cholinomimetic agents. Moreover, tolerance to the anesthetic effect of GBL was found to occur after chronic treatment with this drug. The brain levels of GHB at the time of regaining of the righting reflex were 50% higher in GBL pretreated animals then in controls. Indicating the tolerance to GBL-induced "sleep" is due to a decrease sensitivity of the effector to GHB rather than to a faster inactivation of elimination of the drug. |
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Authors:
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O Giorgi; M C Rubio |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Naunyn-Schmiedeberg's archives of pharmacology Volume: 318 ISSN: 0028-1298 ISO Abbreviation: Naunyn Schmiedebergs Arch. Pharmacol. Publication Date: 1981 Dec |
Date Detail:
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Created Date: 1982-04-20 Completed Date: 1982-04-20 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 0326264 Medline TA: Naunyn Schmiedebergs Arch Pharmacol Country: GERMANY, WEST |
Other Details:
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Languages: eng Pagination: 14-8 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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4-Butyrolactone
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pharmacology* Animals Behavior, Animal / drug effects Choline O-Acetyltransferase / metabolism Corpus Striatum / metabolism Furans / pharmacology* Male Membranes / drug effects Pilocarpine / pharmacology Postural Balance / drug effects Quinuclidines / pharmacology* Quinuclidinyl Benzilate / pharmacology* Rats Rats, Inbred Strains Receptors, Cholinergic / drug effects* Receptors, Muscarinic / drug effects* |
| Chemical | |
Reg. No./Substance:
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0/Furans; 0/Quinuclidines; 0/Receptors, Cholinergic; 0/Receptors, Muscarinic; 6581-06-2/Quinuclidinyl Benzilate; 92-13-7/Pilocarpine; 96-48-0/4-Butyrolactone; EC 2.3.1.6/Choline O-Acetyltransferase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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