Ceftriaxone ameliorates motor deficits and protects dopaminergic neurons in 6-hydroxydopamine-lesioned rats

ACS Chem Neurosci. 2012 Jan 18;3(1):22-30. doi: 10.1021/cn200072h. Epub 2011 Oct 26.


Parkinson's disease is caused by the degeneration of dopaminergic neurons in substantia nigra. There is no current promising treatment for neuroprotection of dopaminergic neurons. Ceftriaxone is a beta-lactam antibiotic and has been reported to offer neuroprotective effects (Rothstein, J.-D., Patel, S., Regan, M.-R., Haenggeli, C., Huang, Y.-H., Bergles, D.-E., Jin, L., Dykes, H.-M., Vidensky, S., Chung, D.-S., Toan, S.-V., Bruijn, L.-I., Su, Z.-Z., Gupta, P., and Fisher, P.-B. (2005) Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression Nature433, 73-77). In the present study, efficacy of ceftriaxone in neuroprotection of dopaminergic neurons and amelioration of motor deficits in a rat model of Parkinson's disease were investigated. Ceftriaxone was administrated in 6-hydroxydopamine-lesioned rats. Using behavioral tests, grip strength and numbers of apomorphine-induced contralateral rotation were declined in the ceftriaxone-treated group. More importantly, cell death of dopaminergic neurons was found to decrease. In addition, both the protein expression and immunoreactivity for GLT-1 were up-regulated. The present results strongly indicate that ceftriaxone is a potential agent in the treatment of Parkinson's disease.

Keywords: Animal model of Parkinson’s disease; antibiotic; basal ganglia; ceftriaxone; degeneration of dopaminergic neurons; glutamate transporter; glutamate transporter subtype 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Blotting, Western
  • Brain / drug effects*
  • Brain / pathology
  • Ceftriaxone / pharmacology*
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / pathology
  • Female
  • Motor Activity / drug effects*
  • Neuroprotective Agents / pharmacology*
  • Oxidopamine / toxicity
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / pathology
  • Rats
  • Rats, Sprague-Dawley


  • Neuroprotective Agents
  • Ceftriaxone
  • Oxidopamine