Document Detail


Glutamate transporter activation enhances nicotine antinociception and attenuates nicotine analgesic tolerance.
MedLine Citation:
PMID:  22027514     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Analgesic tolerance is partially mediated by enhanced glutamatergic transmission in the CNS. β-lactam antibiotics, through glutamate transporter subtype 1 (GLT-1) activation, reduce extracellular glutamate levels and attenuate tolerance to morphine analgesia in rats. Similar to opioids, nicotine has potent analgesic properties that are subject to tolerance. The purpose of this study was to evaluate the effects of ceftriaxone, a β-lactam antibiotic and GLT-1 activator on nicotine antinociception and its tolerance. Rats were pretreated for 5 days with ceftriaxone (200 mg/kg, intraperitoneally) before evaluating their analgesic response to nicotine (1.0 or 2.5 mg/kg, subcutaneously) for seven consecutive days using the tail-flick assay. Ceftriaxone-treated rats displayed an enhanced antinociceptive response to nicotine and unlike saline-injected controls, did not develop tolerance to nicotine's analgesic effects. These results suggest that GLT-1 transporter activation enhances and preserves nicotine antinociception and identify β-lactam antibiotics as potential complementary therapeutic agents for the treatment of chronic pain.
Authors:
Joseph A Schroeder; Katrina F Quick; Paige M Landry; Scott M Rawls
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Neuroreport     Volume:  22     ISSN:  1473-558X     ISO Abbreviation:  Neuroreport     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-17     Completed Date:  2012-03-13     Revised Date:  2014-03-31    
Medline Journal Info:
Nlm Unique ID:  9100935     Medline TA:  Neuroreport     Country:  England    
Other Details:
Languages:  eng     Pagination:  970-3     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Transport System X-AG / metabolism*
Analgesics / pharmacology*
Animals
Ceftriaxone / administration & dosage
Dose-Response Relationship, Drug
Drug Administration Schedule
Drug Tolerance / physiology*
Male
Nicotine / pharmacology*
Pain Measurement / drug effects*
Rats
Rats, Sprague-Dawley
Reaction Time / drug effects
Time Factors
Grant Support
ID/Acronym/Agency:
RC1 DA028153/DA/NIDA NIH HHS; RC1 DA028153/DA/NIDA NIH HHS; RC1 DA028153-01/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acid Transport System X-AG; 0/Analgesics; 54-11-5/Nicotine; 75J73V1629/Ceftriaxone
Comments/Corrections

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