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β-Lactam antibiotic produces a sustained reduction in extracellular glutamate in the nucleus accumbens of rats

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Abstract

We investigated the short- and long-term effects of ceftriaxone on glutamate transporter subtype 1 (GLT-1) transporter activity and extracellular glutamate in the rat nucleus accumbens. Repeated ceftriaxone administration (50, 100 or 200 mg/kg, i.p.) produced a dose-dependent reduction in glutamate levels that persisted for 20 days following discontinuation of drug exposure. The ceftriaxone effect was prevented by the GLT-1 transporter inhibitor dihydrokainate (1 μM, intra-accumbal). These results suggest that β-lactam antibiotics produce an enduring reduction in glutamatergic transmission in the brain reward center.

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References

  • Baker DA, Xi ZX, Shen H, Swanson CJ, Kalivas PW (2002) The origin and neuronal function of in vivo nonsynaptic glutamate. J Neurosci 22:9134–9141

    CAS  PubMed  Google Scholar 

  • Chandrasekar PH, Rolston KV, Smith BR, LeFrock JL (1984) Diffusion of ceftriaxone into the cerebrospinal fluid of adults. J Antimicrob Chemother 14:427–430

    Article  CAS  PubMed  Google Scholar 

  • Chu K, Lee ST, Sinn DI, Ko SY, Kim EH, Kim JM, Kim SJ, Park DK, Jung KH, Song EC, Lee SK, Kim M, Roh JK (2007) Pharmacological induction of ischemic tolerance by glutamate transporter-1 (EAAT2) upregulation. Stroke 38:177–182

    Article  CAS  PubMed  Google Scholar 

  • Granero L, Santiago M, Cano J, Machado A, Peris JE (1995) Analysis of ceftriaxone and ceftazidime distribution in cerebrospinal fluid of and cerebral extracellular space in awake rats by in vivo microdialysis. Antimicrob Agents Chemother 39:2728–2731

    CAS  PubMed  Google Scholar 

  • Kalivas PW (2009) The glutamate homeostasis hypothesis of addiction. Nat Rev Neurosci 10:561–572

    Article  CAS  PubMed  Google Scholar 

  • Knackstedt LA, Melendez RI, Kalivas PW (2010) Ceftriaxone restores glutamate homeostasis and prevents relapse to cocaine seeking. Biol Psychiatry 67(1):81–84

    Article  CAS  PubMed  Google Scholar 

  • Lee SG, Su ZZ, Emdad L, Gupta P, Sarkar D, Borjabad A, Volsky DJ, Fisher PB (2008) Mechanism of ceftriaxone induction of excitatory amino acid transporter-2 expression and glutamate uptake in primary human astrocytes. J Biol Chem 283:13116–13123

    Article  CAS  PubMed  Google Scholar 

  • Lipski J, Wan CK, Bai JZ, Pi R, Li D, Donnelly D (2007) Neuroprotective potential of ceftriaxone in in vitro models of stroke. Neuroscience 146:617–629

    Article  CAS  PubMed  Google Scholar 

  • Miller BR, Dorner JL, Shou M, Sari Y, Barton SJ, Sengelaub DR, Kennedy RT, Rebec GV (2008) Up-regulation of GLT1 expression increases glutamate uptake and attenuates the Huntington’s disease phenotype in the R6/2 mouse. Neuroscience 153:329–337

    Article  CAS  PubMed  Google Scholar 

  • Mitani A, Tanaka K (2003) Functional changes of glial glutamate transporter GLT-1 during ischemia: an in vivo study in the hippocampal CA1 of normal mice and mutant mice lacking GLT-1. J Neurosci 23:7176–7182

    CAS  PubMed  Google Scholar 

  • Nau R, Prange HW, Muth P, Mahr G, Menck S, Kolenda H, Sorgel F (1993) Passage of cefotaxime and ceftriaxone into cerebrospinal fluid of patients with uninflamed meninges. Antimicrob Agents Chemother 37:1518–1524

    CAS  PubMed  Google Scholar 

  • Phillis JW, Ren J, O’Regan MH (2000) Transporter reversal as a mechanism of glutamate release from the ischemic rat cerebral cortex: studies with dl-threo-beta-benzyloxyaspartate. Brain Res 880:224

    Article  CAS  PubMed  Google Scholar 

  • Rawls SM, Zielinski M, Patel H, Sacavage S, Baron DA, Patel D (2010a) β-Lactam antibiotic reduces morphine analgesic tolerance in rats through GLT-1 transporter activation. Drug Alcohol Depend 107:261–263

    Article  CAS  PubMed  Google Scholar 

  • Rawls SM, Baron DA, Kim J (2010b) β-Lactam antibiotic inhibits development of morphine physical dependence in rats. Behav Pharmacol 21:161–164

    Article  CAS  PubMed  Google Scholar 

  • Rothstein JD (1996) Excitotoxicity hypothesis. Neurology 47(Suppl 2):S19–S25

    CAS  PubMed  Google Scholar 

  • Rothstein JD, Dykes-Hoberg M, Pardo CA, Bristol LA, Jin L, Kuncl RW, Kanai Y, Hediger MA, Wang Y, Schielke JP, Welty DF (1996) Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 16:675–686

    Article  CAS  PubMed  Google Scholar 

  • Rothstein JD, Patel S, Regan MR, Haenggeli C, Huang YH, Bergles DE, Jin L, Dykes Hoberg M, Vidensky S, Chung DS, Toan SV, Bruijn LI, Su ZZ, Gupta P, Fisher PB (2005) β-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature 433:73–77

    Article  CAS  PubMed  Google Scholar 

  • Sari Y, Smith KD, Ali PK, Rebec GV (2009) Upregulation of GLT1 attenuates cue-induced reinstatement of cocaine-seeking behavior in rats. J Neurosci 29:9239–9243

    Article  CAS  PubMed  Google Scholar 

  • Werkheiser JL, Rawls SM, Cowan A (2006) Icilin evokes a dose- and time-dependent increase in glutamate within the dorsal striatum of rats. Amino Acids 30:307–309

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was funded by the National Institute on Drug Abuse grants DA025314 (SMR), RC1 DA028153 (SMR) and T32 DA07237-17 (EMU).

Conflict of interest statement

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Temple University Health Sciences Center, 3307 North Broad Street, Philadelphia, PA, 19140, USA

    Bruce A. Rasmussen, David A. Baron, Jae K. Kim & Scott M. Rawls

  2. Department of Pharmacology, Temple University Health Sciences Center, Philadelphia, PA, USA

    Ellen M. Unterwald

  3. Center for Substance Abuse Research, Temple University, Philadelphia, PA, 19140, USA

    Ellen M. Unterwald & Scott M. Rawls

Authors
  1. Bruce A. Rasmussen
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  2. David A. Baron
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  3. Jae K. Kim
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  4. Ellen M. Unterwald
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  5. Scott M. Rawls
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Corresponding author

Correspondence to Scott M. Rawls.

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Rasmussen, B.A., Baron, D.A., Kim, J.K. et al. β-Lactam antibiotic produces a sustained reduction in extracellular glutamate in the nucleus accumbens of rats. Amino Acids 40, 761–764 (2011). https://doi.org/10.1007/s00726-010-0589-0

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  • DOI: https://doi.org/10.1007/s00726-010-0589-0

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