Neurobehavioural and electrophysiological alterations in rats acutely treated with the mitochondrial toxin 3-nitropropionic acid and its functional antagonist, MK-801

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One of the central nervous effects of the mitochondrial toxin 3-nitropropionic acid (3-NP) is to induce glutamatergic over-excitation on NMDA receptors. MK-801 (dizocilpine maleate) as an NMDA antagonist potentially counteracts the nervous system damage caused by 3-NP. In the present study, 3-NP and/or MK-801 were given to rats, and changes in behavioural and electrophysiological parameters were observed. - Adult male Wistar rats (10 in a group) were treated with single doses of 3-NP (20 mg/kg) and MK-801(0.4 mg/kg) by intraperitoneal injection. Ten rats received 3-NP first and MK-801 30 minutes later, and another 10 rats were given these drugs in a reverse combination. Ten control rats were injected with saline. To test whether 3-NP-induced deficits in sensorimotor gating similar to those observed in Huntington's disease, acoustic startle response with or without pre-pulse inhibition was measured. - 3-NP was found to decrease, but MK-801 and 3NP+MK801 combination treatment was found to increase, the number of the noise-positive responses. MK801+3NP administration caused no change. The number of noise positive responses following prepulse inhibition increased after 3-NP and 3-NP+MK-801 treatment, and did not change after MK-801 and MK801+3NP treatment. MK-801 relatively decreased, 3-NP relatively increased climbing time, in both combination groups it returned close to the level of the control group. The rats were then anesthetized with urethane and electrophysiological investigation was done. MK-801 and 3NP+MK801 treatment caused latency increase, but the reverse combination caused latency decrease, of the somatosensory evoked potential. The duration of the response decreased significantly in MK-801 and in 3-NP treated rats and in those treated with the combination of 3NP-MK801. In the tail nerve, conduction velocity was increased by MK-801 and MK801+3NP combination. According to these experiments, we can assume that MK-801 does not prevent the NMDA mediated neurodegenerative effects of 3-NP efficiently enough to be used for compensating the existing damages, although we need more examinations to prove this.

Original languageEnglish
Pages (from-to)173-178
Number of pages6
JournalHomeostasis in Health and Disease
Issue number4
Publication statusPublished - Nov 1 2005



  • 3-nitropropionic acid
  • Acoustic startle response
  • Cortical evoked response
  • Nerve action potential
  • Neurotoxicity
  • Rat

ASJC Scopus subject areas

  • Neuroscience(all)
  • Psychiatry and Mental health

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