Document Detail


The beta-lactam antibiotic ceftriaxone inhibits physical dependence and abstinence-induced withdrawal from cocaine, amphetamine, methamphetamine, and clorazepate in planarians.
MedLine Citation:
PMID:  18342307     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ceftriaxone (a beta-lactam antibiotic) has recently been identified as having the rare ability to increase the expression and functional activity of the glutamate transporter subtype 1 (GLT-1) in rat spinal cord cultures. GLT-1 has been implicated in diverse neurological disorders and in opioid dependence and withdrawal. It has been speculated that it might also be involved in the physical dependence and withdrawal of other abused drugs, but demonstration of this property can be difficult in mammalian models. Here, we demonstrate for the first time using a planarian model that ceftriaxone attenuates both the development of physical dependence and abstinence-induced withdrawal from cocaine, amphetamine, methamphetamine, and a benzodiazepine (clorazepate) in a concentration-related manner. These results suggest that physical dependence and withdrawal from several drugs involve a common - beta-lactam-sensitive - mechanism in planarians. If these findings can be shown to extend to mammals, beta-lactam antibiotics might represent a novel pharmacotherapy or adjunct approach for treating drug abuse or serve as a template for drug discovery efforts aimed at treating drug abuse, recovery from drug abuse, or ameliorating the withdrawal from chronic use of therapeutic medications.
Authors:
Scott M Rawls; Federica Cavallo; Anna Capasso; Zhe Ding; Robert B Raffa
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-02-17
Journal Detail:
Title:  European journal of pharmacology     Volume:  584     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-04-08     Completed Date:  2008-07-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  278-84     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 N. Broad Street, Philadelphia, PA 19140, USA.
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MeSH Terms
Descriptor/Qualifier:
Amphetamine / adverse effects*
Amphetamine-Related Disorders / prevention & control
Animals
Anti-Bacterial Agents / pharmacology*
Ceftriaxone / pharmacology*
Clorazepate Dipotassium / adverse effects*
Cocaine / adverse effects*
Cocaine-Related Disorders / prevention & control
Dose-Response Relationship, Drug
Excitatory Amino Acid Transporter 2 / drug effects,  metabolism
Methamphetamine / adverse effects*
Models, Animal
Motor Activity / drug effects
Planarians
Substance Withdrawal Syndrome / metabolism,  prevention & control*
Substance-Related Disorders / metabolism,  prevention & control*
Time Factors
Grant Support
ID/Acronym/Agency:
DA022694/DA/NIDA NIH HHS; R01-DA15378/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Excitatory Amino Acid Transporter 2; 300-62-9/Amphetamine; 50-36-2/Cocaine; 537-46-2/Methamphetamine; 57109-90-7/Clorazepate Dipotassium; 73384-59-5/Ceftriaxone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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