Cefazolin and ceftriaxone attenuate the cue-primed reinstatement of alcohol-seeking

Alcohol consumption and the reinstatement of alcohol-seeking rely on glutamate and GABA transmission. Modulating these neurotransmitters may be a viable treatment strategy to prevent alcohol relapse. N-acetylcysteine (NAC) and the antibiotic ceftriaxone (CEF) alter the glial reuptake and release of...

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Main Authors: Ana eWeiland, Steven eGarcia, Lori A Knackstedt
Format: Article
Language:English
Published: Frontiers Media S.A. 2015-03-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fphar.2015.00044/full
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author Ana eWeiland
Steven eGarcia
Lori A Knackstedt
author_facet Ana eWeiland
Steven eGarcia
Lori A Knackstedt
author_sort Ana eWeiland
collection DOAJ
description Alcohol consumption and the reinstatement of alcohol-seeking rely on glutamate and GABA transmission. Modulating these neurotransmitters may be a viable treatment strategy to prevent alcohol relapse. N-acetylcysteine (NAC) and the antibiotic ceftriaxone (CEF) alter the glial reuptake and release of glutamate while the antibiotic cefazolin (CEFAZ) modulates GABA signaling without affecting glutamate. Here we used the extinction-reinstatement model of relapse to test the ability of these compounds to attenuate the reinstatement of alcohol-seeking. Male Sprague-Dawley rats were trained to self-administer 20% (v/v) alcohol in the home cage using an intermittent schedule (24 hr on, 24 hr off) for 12 sessions. Subsequently, animals self-administered alcohol during daily 45-min operant sessions for 26 sessions, followed by extinction training. We tested whether chronic administration of NAC, CEF or CEFAZ attenuated the cue-primed reinstatement of alcohol-seeking. CEF and CEFAZ attenuated cue-primed reinstatement of alcohol-seeking while NAC had no effect. We subsequently investigated whether CEF and CEFAZ alter the self-administration of sucrose and chow pellets and if CEFAZ attenuates the reinstatement of cocaine-seeking. The operant self-administration of regular chow and sucrose was not altered by either CEF or CEFAZ. CEFAZ had no effect on cocaine reinstatement, a behavior that has been strongly tied to altered glutamate homeostasis in the nucleus accumbens. Thus the ability of CEFAZ to attenuate alcohol reinstatement likely does not involve the glial modulation of glutamate levels. The dampening of GABA transmission may be a common mechanism of action of cefazolin and ceftriaxone.
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spelling doaj.art-bc5c256cbf3b4de09ae7ebd084c6e5ac2022-12-22T00:54:43ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122015-03-01610.3389/fphar.2015.00044135276Cefazolin and ceftriaxone attenuate the cue-primed reinstatement of alcohol-seekingAna eWeiland0Steven eGarcia1Lori A Knackstedt2College of CharlestonUniversity of FloridaUniversity of FloridaAlcohol consumption and the reinstatement of alcohol-seeking rely on glutamate and GABA transmission. Modulating these neurotransmitters may be a viable treatment strategy to prevent alcohol relapse. N-acetylcysteine (NAC) and the antibiotic ceftriaxone (CEF) alter the glial reuptake and release of glutamate while the antibiotic cefazolin (CEFAZ) modulates GABA signaling without affecting glutamate. Here we used the extinction-reinstatement model of relapse to test the ability of these compounds to attenuate the reinstatement of alcohol-seeking. Male Sprague-Dawley rats were trained to self-administer 20% (v/v) alcohol in the home cage using an intermittent schedule (24 hr on, 24 hr off) for 12 sessions. Subsequently, animals self-administered alcohol during daily 45-min operant sessions for 26 sessions, followed by extinction training. We tested whether chronic administration of NAC, CEF or CEFAZ attenuated the cue-primed reinstatement of alcohol-seeking. CEF and CEFAZ attenuated cue-primed reinstatement of alcohol-seeking while NAC had no effect. We subsequently investigated whether CEF and CEFAZ alter the self-administration of sucrose and chow pellets and if CEFAZ attenuates the reinstatement of cocaine-seeking. The operant self-administration of regular chow and sucrose was not altered by either CEF or CEFAZ. CEFAZ had no effect on cocaine reinstatement, a behavior that has been strongly tied to altered glutamate homeostasis in the nucleus accumbens. Thus the ability of CEFAZ to attenuate alcohol reinstatement likely does not involve the glial modulation of glutamate levels. The dampening of GABA transmission may be a common mechanism of action of cefazolin and ceftriaxone.http://journal.frontiersin.org/Journal/10.3389/fphar.2015.00044/fullCefazolinCeftriaxoneCocaineAddictionGABAGlutamate
spellingShingle Ana eWeiland
Steven eGarcia
Lori A Knackstedt
Cefazolin and ceftriaxone attenuate the cue-primed reinstatement of alcohol-seeking
Frontiers in Pharmacology
Cefazolin
Ceftriaxone
Cocaine
Addiction
GABA
Glutamate
title Cefazolin and ceftriaxone attenuate the cue-primed reinstatement of alcohol-seeking
title_full Cefazolin and ceftriaxone attenuate the cue-primed reinstatement of alcohol-seeking
title_fullStr Cefazolin and ceftriaxone attenuate the cue-primed reinstatement of alcohol-seeking
title_full_unstemmed Cefazolin and ceftriaxone attenuate the cue-primed reinstatement of alcohol-seeking
title_short Cefazolin and ceftriaxone attenuate the cue-primed reinstatement of alcohol-seeking
title_sort cefazolin and ceftriaxone attenuate the cue primed reinstatement of alcohol seeking
topic Cefazolin
Ceftriaxone
Cocaine
Addiction
GABA
Glutamate
url http://journal.frontiersin.org/Journal/10.3389/fphar.2015.00044/full
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