title: Ceftriaxone prevents the induction of cocaine sensitization and produces enduring attenuation of cue- and cocaine-primed reinstatement of cocaine-seeking.
abstract: Ceftriaxone is a beta-lactam antibiotic which has been found to increase the expression and function of the major glutamate transporter, GLT-1. It has previously been shown that GLT-1 expression is decreased in the nucleus accumbens following cocaine self-administration and extinction training; ceftriaxone given in the days immediately prior to reinstatement testing attenuates both cue- and cocaine-primed reinstatement. Here we tested the ability of ceftriaxone pre-treatment (for 5 days prior to the first cocaine exposure) to prevent the induction of cocaine sensitization and the acquisition of cocaine self-administration. We also tested whether ceftriaxone administered only during self-administration attenuates the reinstatement of extinguished cocaine-seeking. We found that ceftriaxone did not affect the acquisition of cocaine self-administration but was able to attenuate reinstatement weeks after ceftriaxone administration ceased. This attenuation in reinstatement was accompanied by a restoration of GLT-1 expression in the nucleus accumbens. Ceftriaxone also attenuated locomotor behavior following the first cocaine injection and prevented the induction of cocaine but not caffeine sensitization. While ceftriaxone-treated animals did not sensitize to caffeine, they displayed reduced caffeine-induced locomotion following repeated caffeine treatment, indicating a possible dopaminergic effect of ceftriaxone. Taken together, these results indicate that ceftriaxone produces enduring changes in glutamate homeostasis in the nucleus accumbens which counteract addiction-related behaviors.
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Ilan
authors.initials: I
authors.lastname: Sondheimer
authors.forename: Lori A
authors.initials: LA
authors.lastname: Knackstedt
mesh_terms: D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000008:administration & dosage*; D000818:Animals; D002443:Ceftriaxone / Q000627:therapeutic use*; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000517:prevention & control* / Q000523:psychology; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D004195:Disease Models, Animal; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: D000779:Anesthetics, Local; D027341:Excitatory Amino Acid Transporter 1; D002443:Ceftriaxone; D003042:Cocaine