Neuroprotective effects of agmatine in mice infused with a single intranasal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

Behav Brain Res. 2012 Dec 1;235(2):263-72. doi: 10.1016/j.bbr.2012.08.017. Epub 2012 Aug 17.


We have recently demonstrated that rodents treated intranasally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) suffered impairments in olfactory, cognitive, emotional and motor functions associated with time-dependent disruption of dopaminergic neurotransmission in different brain structures conceivably analogous to those observed during different stages of Parkinson's disease (PD). Agmatine, an endogenous arginine metabolite, has been proposed as a novel neuromodulator that plays protective roles in several models of neuronal cellular damage. In the present study we demonstrated that repeated treatment with agmatine (30 mg/kg, i.p.) during 5 consecutive days increased the survival rate (from 40% to 80%) of 15-month-old C57BL/6 female mice infused with a single intranasal (i.n.) administration of MPTP (1 mg/nostril), improving the general neurological status of the surviving animals. Moreover, pretreatment with agmatine was found to attenuate short-term social memory and locomotor activity impairments observed at different periods after i.n. MPTP administration. These behavioral benefits of exogenous agmatine administration were accompanied by a protection against the MPTP-induced decrease of hippocampal glutamate uptake and loss of dopaminergic neurons in the substantia nigra pars compacta of aging mice, without altering brain monoamine oxidase B (MAO-B) activity. These results provide new insights in experimental models of PD, indicating that agmatine represents a potential therapeutic tool for the management of cognitive and motor symptoms of PD, together with its neuroprotective effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / administration & dosage*
  • Administration, Intranasal / methods
  • Agmatine / therapeutic use*
  • Analysis of Variance
  • Animals
  • Disease Models, Animal
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / pathology
  • Drug Administration Schedule
  • Drug Interactions
  • Exploratory Behavior / drug effects
  • Female
  • Glutamic Acid / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity
  • Neurologic Examination
  • Neuroprotective Agents / therapeutic use*
  • Parkinsonian Disorders / etiology
  • Parkinsonian Disorders / mortality
  • Parkinsonian Disorders / pathology
  • Parkinsonian Disorders / prevention & control*
  • Recognition, Psychology / drug effects
  • Social Behavior
  • Substantia Nigra / drug effects
  • Substantia Nigra / pathology
  • Survival Analysis
  • Tritium / metabolism
  • Tyrosine 3-Monooxygenase / metabolism


  • Neuroprotective Agents
  • Tritium
  • Glutamic Acid
  • Agmatine
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Tyrosine 3-Monooxygenase