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Ceftriaxone attenuates cocaine relapse after abstinence through modulation of nucleus accumbens AMPA subunit expression.
Eur Neuropsychopharmacol 2016; 26(2):186-194EN

Abstract

Using the extinction-reinstatement model of cocaine relapse, we and others have demonstrated that the antibiotic ceftriaxone attenuates cue- and cocaine-primed reinstatement of cocaine-seeking. Reinstatement is contingent on the release of glutamate in the nucleus accumbens core (NAc) and manipulations that reduce glutamate efflux or block post-synaptic glutamate receptors attenuate reinstatement. We have demonstrated that the mechanism of action by which ceftriaxone attenuates reinstatement involves increased NAc GLT-1 expression and a reduction in NAc glutamate efflux during reinstatement. Here we investigated the effects of ceftriaxone (100 and 200 mg/kg) on context-primed relapse following abstinence without extinction training and examined the effects of ceftriaxone on GluA1, GluA2 and GLT-1 expression. We conducted microdialysis during relapse to determine if an increase in NAc glutamate accompanies relapse after abstinence and whether ceftriaxone blunts glutamate efflux. We found that both doses of ceftriaxone attenuated relapse. While relapse was accompanied by an increase in NAc glutamate, ceftriaxone (200 mg/kg) was unable to significantly reduce NAc glutamate efflux during relapse despite its ability to upregulate GLT-1. GluA1 was reduced in the NAc by both doses of ceftriaxone while GluA2 expression was unchanged, indicating that ceftriaxone altered AMPA subunit composition following cocaine. Finally, GLT-1 was not altered in the PFC by ceftriaxone. These results indicate that it is possible to attenuate context-primed relapse to cocaine-seeking through modification of post-synaptic receptor properties without attenuating glutamate efflux during relapse. Furthermore, increasing NAc GLT-1 protein expression is not sufficient to attenuate glutamate efflux.

Authors+Show Affiliations

Psychology Department, University of Florida, Gainesville, FL, United States.Psychology Department, University of Florida, Gainesville, FL, United States.Psychology Department, University of Florida, Gainesville, FL, United States. Electronic address: knack@ufl.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

26706696

Citation

LaCrosse, Amber L., et al. "Ceftriaxone Attenuates Cocaine Relapse After Abstinence Through Modulation of Nucleus Accumbens AMPA Subunit Expression." European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, vol. 26, no. 2, 2016, pp. 186-194.
LaCrosse AL, Hill K, Knackstedt LA. Ceftriaxone attenuates cocaine relapse after abstinence through modulation of nucleus accumbens AMPA subunit expression. Eur Neuropsychopharmacol. 2016;26(2):186-194.
LaCrosse, A. L., Hill, K., & Knackstedt, L. A. (2016). Ceftriaxone attenuates cocaine relapse after abstinence through modulation of nucleus accumbens AMPA subunit expression. European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, 26(2), pp. 186-194. doi:10.1016/j.euroneuro.2015.12.022.
LaCrosse AL, Hill K, Knackstedt LA. Ceftriaxone Attenuates Cocaine Relapse After Abstinence Through Modulation of Nucleus Accumbens AMPA Subunit Expression. Eur Neuropsychopharmacol. 2016;26(2):186-194. PubMed PMID: 26706696.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ceftriaxone attenuates cocaine relapse after abstinence through modulation of nucleus accumbens AMPA subunit expression. AU - LaCrosse,Amber L, AU - Hill,Kristine, AU - Knackstedt,Lori A, Y1 - 2015/12/10/ PY - 2015/09/22/received PY - 2015/11/21/revised PY - 2015/12/04/accepted PY - 2015/12/27/entrez PY - 2015/12/27/pubmed PY - 2016/12/15/medline KW - Cocaine KW - GLT-1 KW - GluA1 KW - Glutamate KW - Nucleus accumbens KW - Relapse SP - 186 EP - 194 JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology JO - Eur Neuropsychopharmacol VL - 26 IS - 2 N2 - Using the extinction-reinstatement model of cocaine relapse, we and others have demonstrated that the antibiotic ceftriaxone attenuates cue- and cocaine-primed reinstatement of cocaine-seeking. Reinstatement is contingent on the release of glutamate in the nucleus accumbens core (NAc) and manipulations that reduce glutamate efflux or block post-synaptic glutamate receptors attenuate reinstatement. We have demonstrated that the mechanism of action by which ceftriaxone attenuates reinstatement involves increased NAc GLT-1 expression and a reduction in NAc glutamate efflux during reinstatement. Here we investigated the effects of ceftriaxone (100 and 200 mg/kg) on context-primed relapse following abstinence without extinction training and examined the effects of ceftriaxone on GluA1, GluA2 and GLT-1 expression. We conducted microdialysis during relapse to determine if an increase in NAc glutamate accompanies relapse after abstinence and whether ceftriaxone blunts glutamate efflux. We found that both doses of ceftriaxone attenuated relapse. While relapse was accompanied by an increase in NAc glutamate, ceftriaxone (200 mg/kg) was unable to significantly reduce NAc glutamate efflux during relapse despite its ability to upregulate GLT-1. GluA1 was reduced in the NAc by both doses of ceftriaxone while GluA2 expression was unchanged, indicating that ceftriaxone altered AMPA subunit composition following cocaine. Finally, GLT-1 was not altered in the PFC by ceftriaxone. These results indicate that it is possible to attenuate context-primed relapse to cocaine-seeking through modification of post-synaptic receptor properties without attenuating glutamate efflux during relapse. Furthermore, increasing NAc GLT-1 protein expression is not sufficient to attenuate glutamate efflux. SN - 1873-7862 UR - https://www.unboundmedicine.com/medline/citation/26706696/Ceftriaxone_attenuates_cocaine_relapse_after_abstinence_through_modulation_of_nucleus_accumbens_AMPA_subunit_expression_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924-977X(15)00405-8 DB - PRIME DP - Unbound Medicine ER -