title: Ceftriaxone attenuates acquisition and facilitates extinction of cocaine-induced suppression of saccharin intake in C57BL/6J mice.
abstract: Growing evidence implicates glutamate homeostasis in a number of behaviors observed in addiction such as acquisition of drug taking, motivation, and reinstatement. To date, however, the role of glutamate homeostasis in the avoidance of natural rewards due to exposure to drugs of abuse has received little attention. The aim of the current study was to evaluate the beta-lactam antibiotic, ceftriaxone, which has been shown to normalize disrupted glutamate homeostasis associated with exposure to drugs of abuse, in cocaine-induced suppression of saccharin intake in C57BL/6J mice. Briefly, C57BL/6J mice received daily injections of either 200mg/kg ceftriaxone or saline. Mice were then given access to 0.15% saccharin for 1h and immediately injected intraperitoneally with either saline or 30 mg/kg cocaine; taste-drug pairings occurred every 24h for 5 trials followed by a final CS only trial. One week following taste-drug pairings, extinction was evaluated in a series of one- and two-bottle saccharin intake tests. Individual differences in cocaine-induced suppression were observed (i.e., low and high suppressors) with differential effects of ceftriaxone. Ceftriaxone delayed suppression of saccharin intake in high suppressors but prevented suppression in low suppressors. In addition, ceftriaxone history facilitated extinction in the high suppressors. These data suggest that changes in glutamate homeostasis may be involved in the formation and expression of cocaine-induced suppression of saccharin intake in mice.
authors.affiliation: The Pennsylvania State University College of Medicine, Department of Neural and Behavioral Sciences, 500 University Drive, Hershey, PA 17033, USA. Electronic address: csf5@psu.edu.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Freet
authors.affiliation: The Lincoln University, 1570 Baltimore Pike, PA 19352, USA.
authors.forename: Antoneal L
authors.initials: AL
authors.lastname: Lawrence
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002443:Ceftriaxone / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D005108:Extinction, Psychological / Q000187:drug effects*; D005518:Food Preferences / Q000187:drug effects*; D007206:Individuality; D007266:Inhibition, Psychological; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012439:Saccharin / Q000008:administration & dosage*; D012646:Self Administration; D018709:Statistics, Nonparametric; D013549:Sweetening Agents / Q000008:administration & dosage*; D013649:Taste / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D018765:Dopamine Uptake Inhibitors; D013549:Sweetening Agents; D002443:Ceftriaxone; D012439:Saccharin; D003042:Cocaine
keywords: Addiction; Glia; Glutamate; Natural rewards; Reward comparison