Ceftriaxone upregulates the glutamate transporter in medial prefrontal cortex and blocks reinstatement of methamphetamine seeking in a condition place preference paradigm

Osama A. Abulseoud, Joseph D. Miller, Jinhua Wu, Doo Sup Choi, Daniel P. Holschneider

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Glutamate signaling plays an essential role in drug-seeking behavior. Using reinstatement of conditioned place preference (CPP), we determined whether ceftriaxone, a β-lactam antibiotic known to increase the expression and activity of the glutamate transporter (EAAT 2) on glial cells, blocks methamphetamine-triggered reinstatement of CPP. Rats acquired methamphetamine CPP following 7 consecutive days of conditioning, during which each animal received pairings of alternating morning methamphetamine (2.5 mg/kg, IP) and afternoon saline (IP). Animals showing CPP were successfully extinguished with repeated twice daily saline administration over a 7-day period. Ceftriaxone (200 mg/kg, IP) was administered (vs. saline) once a day for 7 days during the extinction period. Upon successful extinction, animals received a single dose of methamphetamine (2.5 mg/kg, IP) for reinstatement and were tested for CPP one day later. Using real time PCR, EAAT 2 mRNA levels in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) were quantified in response to ceftriaxone. Ceftriaxone blocked methamphetamine-triggered reinstatement of CPP and significantly increased EAAT 2 mRNA levels in the mPFC, with a trend towards significance in the NAc. In conclusion, Ceftriaxone modulated the expression of the glutamate transporter in a critical region of the cortico-striatal addiction circuitry and attenuated drug-seeking behavior in rats. Further research is needed to test the efficacy of compounds targeting the EAAT 2 in human methamphetamine-dependent users.

Original languageEnglish (US)
Pages (from-to)14-21
Number of pages8
JournalBrain Research
Volume1456
DOIs
StatePublished - May 25 2012

Keywords

  • Addiction
  • Ceftriaxone
  • Conditioned place preference
  • Excitatory amino acid transporter
  • Glutamate
  • Glutamate transporter
  • Methamphetamine
  • Relapse

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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