title: Glutamate transporter subtype 1 (GLT-1) activator ceftriaxone attenuates amphetamine-induced hyperactivity and behavioral sensitization in rats.
abstract: BACKGROUND
  The β-lactam antibiotic and glutamate transporter subtype 1 (GLT-1) activator ceftriaxone prevents relapse to cocaine-seeking and inhibits morphine-induced physical dependence and tolerance in rats, but its efficacy against amphetamine-induced behaviors is unknown.
  
  
  METHODS
  Here, we tested the hypothesis that ceftriaxone (200mg/kg, i.p.) inhibits hyperactivity produced by acute amphetamine administration (2mg/kg, i.p.) and sensitization of hyperactivity induced by repeated amphetamine exposure (2mg/kg, i.p.). For acute experiments, rats treated with ceftriaxone for 5 days were injected with amphetamine or saline on day 6.
  
  
  RESULTS
  Amphetamine elicited less ambulatory and stereotypical activity in ceftriaxone-treated rats than in ceftriaxone-naïve rats. For chronic experiments, rats injected with ceftriaxone or saline for 8 days were also injected with amphetamine or saline on days 6-8 and then challenged with amphetamine 5 days later. Amphetamine produced greater ambulatory and stereotypical activity in amphetamine-pretreated rats than in rats previously naïve to amphetamine. Amphetamine challenge produced less ambulatory and stereotypical activity in rats pretreated with a combination of ceftriaxone (200mg/kg) and amphetamine than in rats pretreated with only amphetamine.
  
  
  CONCLUSIONS
  The present demonstration that ceftriaxone attenuates amphetamine-induced hyperactivity and behavioral sensitization suggests its documented efficacy against adverse cocaine and morphine effects extends to amphetamine.
authors.affiliation: Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 North Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Rasmussen
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Unterwald
authors.forename: Scott M
authors.initials: SM
authors.lastname: Rawls
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002443:Ceftriaxone / Q000494:pharmacology*; D059333:Central Nervous System Sensitization / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D027342:Excitatory Amino Acid Transporter 2 / Q000819:agonists*; D006948:Hyperkinesis / Q000139:chemically induced* / Q000188:drug therapy; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000697:Central Nervous System Stimulants; D027342:Excitatory Amino Acid Transporter 2; D002443:Ceftriaxone; D000661:Amphetamine