Altered Open Field Behavior in Rats Induced by Acute Administration of 3-Nitropropionic Acid: Possible Glutamatergic and Dopaminergic Involvement


3-nitropropionic acid (3-NP), a substance used for modelling Huntington’s disease, was given to male Wistar rats in a single 20 mg/kg b.w. dose, and the resulting behavioral alterations in spontaneous locomotor activity were measured after 30 minutes. To detect the involvement of neurotransmitter systems in this immediate effect, the NMDA antagonist MK-801 (0.8 mg/kg); as well as an agonist, quinpirole (QP, 5 mg/kg) and an antagonist, sulpiride (SP, 80 mg/kg) of the dopamine D2 receptors, were given before 3-NP to separate groups of rats. Controls were given saline. All substances were injected ip. 3-NP decreased the rats’ locomotor, especially vertical, activity, whereas local activity was increased. Based on the further changes of 3-NP effects in the combination groups it could be concluded that dopaminergic rather than glutamatergic mechanisms were possibly involved in the acute behavioral effect of 3-NP.


  1. 1.

    Alexi, T., Borlongan, C. V., Faull, R. L. M., Williams, C. E., Clark, R. G., Gluckmann, P. D., Hughes, P. E. (2000) Neuroprotective strategies for basal ganglia degeneration: Parkinson’s and Huntington’s diseases. Prog. Neurobiol. 60, 409–470.

    CAS  Article  Google Scholar 

  2. 2.

    Authier, N., Dupuis, E., Kwasiborski, A., Eschalier, A., Coudoré, F. (2002) Behavioural assessment of dimethylsulfoxide neurotoxicity in rats. Toxicol. Lett. 132, 117–121.

    CAS  Article  Google Scholar 

  3. 3.

    Bast, T., da Silva, B. M., Morris, R. G. (2005) Distinct contributions of hippocampal NMDA and AMPA receptors to encoding and retrieval of one-trial place memory. J. Neurosci. 25, 5845–5856.

    CAS  Article  Google Scholar 

  4. 4.

    Beal, M. F., Brouillet, E., Jenkins, B. G., Ferrante, R. J., Kowall, N. W., Miller, J. M., Storey, E., Srivastava, R., Rosen, B. R., Hyman, B. T. (1993) Neurochemical and histological characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitroproprionic acid. J. Neurosci. 13, 4181–4192.

    CAS  Article  Google Scholar 

  5. 5.

    Borlongan, C. V., Koutouzis, T. K., Randall, T. S., Freeman, B., Cahill, D. W., Sanberg, P. R. (1995) Systemic 3-nitropropionic acid: behavioural deficits and striatal damage in adult rats. Brain Res. Bull. 36, 549–556.

    CAS  Article  Google Scholar 

  6. 6.

    Borlongan, C. V., Koutouzis, T. K., Sanberg, P. R. (1997) 3-nitropropionic acid animal model and Huntington’s Disease. Neurosci. Biobehav. Res. 21, 289–293.

    CAS  Article  Google Scholar 

  7. 7.

    Brouillet, E., Jenkins, B. G., Hyman, B. T., Ferrante, R. J., Kowall, N. W., Srivastava, R., Roy, D. S., Rosen, B. R., Beal, M. F. (1993) Age-dependent vulnerability of the striatum to the mitochondrial toxin 3-nitropropionic acid. J. Neurochem. 60, 356–359.

    CAS  Article  Google Scholar 

  8. 8.

    Gao, X., Xu, X., Pang, J., Zhang, C., Ding, J. M., Peng, X., Liu, Y., Cao, J. M. (2007) NMDA receptor activation induces mitochondrial dysfunction, oxidative stress and apoptosis in cultured neonatal rat cardiomyocytes. Physiol. Res. 56, 559–569.

    CAS  PubMed  Google Scholar 

  9. 9.

    Garcia, M., Vanhoutte, P., Pages, C., Besson, M. J., Brouillet, E., Caboche, J. (2002) The mitochondrial toxin 3-nitropropionic acid induces striatal neurodegeneration via a c-Jun N-terminal kinase/c-Jun modul. J. Neurosci. 22, 2174–2184.

    CAS  Article  Google Scholar 

  10. 10.

    Hersch, S. M., Ciliax, B. J., Gutekunst, C-A., Rees, H. D., Heilman, C. J., Yung, K. K. L., Bolam, J. P., Ince, E., Yi, H., Levey, A. I. (1995) Electron microscopic analysis of D1 and D2 dopamine receptor proteins in the dorsal striatum and their synaptic relationships with motor corticostriatal afferents. J. Neurosci. 15, 5222–5237.

    CAS  Article  Google Scholar 

  11. 11.

    Horváth, Zs. C., Czopf, J., Buzsáki, Gy. (1997) MK-801 induced neuronal damage in rats. Brain Res. 753, 181–195.

    Article  Google Scholar 

  12. 12.

    Kodsi, M. H., Swerdlow, N. R. (1997) Mitochondrial toxin 3-nitropropionic acid produces startle reflex abnormalities and striatal damage in rats that model some features of Huntington’s disease. Neurosci. Lett. 231, 103–107.

    CAS  Article  Google Scholar 

  13. 13.

    Koyuncuoglu, H., Kara, I., Günel, M. A., Nurten, A., Yamantürk, P. (1998) N-Methyl-D-aspartate antagonists, glutamate release inhibitors, 4-aminopyridine at neuromuscular transmission. Pharmacol. Res. 37, 485–491.

    CAS  Article  Google Scholar 

  14. 14.

    Lee, W. T., Shen, Y. Z., Chang, C. (2000) Neuroprotective effect of lamotrigine and MK-801 on rat brain lesions induced by 3-nitropropionic acid: evaluation by magnetic resonance imaging and in vivo proton magnetic resonance spectroscopy. Neuroscience 95, 89–95.

    CAS  Article  Google Scholar 

  15. 15.

    Lee, W. T., Yin, H. S., Shen, Y. Z. (2002) The mechanism of neuronal death produced by mitochondrial toxin 3-nitropropionic acid: the roles of N-methyl-D-aspartate glutamate receptors and mitochondrial calcium overload. Neuroscience 112, 707–716.

    CAS  Article  Google Scholar 

  16. 16.

    Ludolph, A. C., He, F., Spencer, P. S., Hammerstad, J., Sabri, M. (1991) 3-Nitropropionic acid-exogenous animal neurotoxin and possible human striatal toxin. Can. J. Neurol. Sci. 18, 492–498.

    CAS  Article  Google Scholar 

  17. 17.

    Lukács, A., Szabó, A., Nagymajtényi, L. (2005) Changes in neurobehavioural parameters and spontaneous cortical activity in rats after acute single and combined exposure by 3-nitropropionic acid and MK-801. Homeostasis 43, 169–172.

    Google Scholar 

  18. 18.

    Lukács, A., Szabó, A., Vezér, T., Papp, A. (2006) The acute effects of 3-nitropropionic acid on the behavior and spontaneous cortical electrical activity of rats. Acta Neurobiol. Exp. 66, 227–233.

    Google Scholar 

  19. 19.

    Lukács, A., Szabó, A., Vezér, T., Papp, A. (2007) Immediate and acute neurobehavioural effects of a glutamate agonist and antagonist in rats. Clin. Neurosci. 60, 42.

    Google Scholar 

  20. 20.

    Miller, A. D., Forster, G. L., Metcalf, K. M., Blaha, C. D. (2002) Excitotoxic lesions of the pedunculopontine differentially mediate morphine- and d-amphetamine-evoked striatal dopamine efflux and behaviors. Neuroscience 111, 351–362.

    CAS  Article  Google Scholar 

  21. 21.

    Nishino, H., Kumazaki, M., Fukuda, A., Fujimoto, I., Shimano, Y., Hida, H., Sakurai, T., Deshpande, S. B., Shimizu, H., Morikawa, S., Inubushi, T. (1997) Acute 3-nitropropionic acid intoxication induces striatal astrocytic cell death and dysfunction of the blood-brain barrier: involvement of dopamine toxicity. Neurosci. Res. 27, 343–355.

    CAS  Article  Google Scholar 

  22. 22.

    Pang, Z., Geddes, J. W. (1997) Mechanisms of cell death induced by the mitochondrial toxin 3-nitropropionic acid: acute excitotoxic necrosis and delayed apoptosis. J. Neurosci. 17, 3064–3073.

    CAS  Article  Google Scholar 

  23. 23.

    Park, C. K., Nehls, D. G., Graham, D. I., Teasdale, G. M., McCulloch, J. (1988) The glutamate antagonist MK-801 reduces focal ischemic brain damage in the rat. Ann. Neurol. 24, 543–551.

    CAS  Article  Google Scholar 

  24. 24.

    Schulz, J. B., Matthews, R. T., Henshaw, D. R., Beal, M. F. (1996) Neuroprotective strategies for treatment of lesions produced by mitochondrial toxins: implications for neurodegenerative diseases. Neuroscience 71, 1043–1048.

    CAS  Article  Google Scholar 

  25. 25.

    Seaman, R. L. (2000) Effects of acute systemic 3-nitropropionic acid administration on rat activity and acoustic startle. Neurosci. Lett. 280, 183–186.

    CAS  Article  Google Scholar 

  26. 26.

    Sedelis, M., Schwarting, R. K., Huston, J. P. (2001) Behavioral phenotyping of the MPTP mouse model of Parkinson’s disease. Behav. Brain Res. 125, 109–125.

    CAS  Article  Google Scholar 

  27. 27.

    Swerdlow, N. R., Paulsen, J., Braff, D. L., Butters, N., Geyer, M. A., Swenson, M. R. (1995) Impaired prepulse inhibition of acoustic and tactile startle in patients with Huntington’s disease. J. Neurol. Neurosurg. Psychiatry 58, 192–200.

    CAS  Article  Google Scholar 

  28. 28.

    Szabó, A., Papp, A. (2003) Instantaneous and subacute functional neurotoxic effects elicited in rats by 3-nitropropionic acid. Clin. Neurosci. 56, 84.

    Google Scholar 

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Lukács, A., Szabó, A., Papp, A. et al. Altered Open Field Behavior in Rats Induced by Acute Administration of 3-Nitropropionic Acid: Possible Glutamatergic and Dopaminergic Involvement. BIOLOGIA FUTURA 60, 359–367 (2009).

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  • 3-nitropropionic acid
  • locomotor activity
  • open field
  • rat