Neurobehavioural and Electrophysiological Alterations in Rats Acutely Treated with the Neurodegenerative 3-Nitropropionic Acid and its Functional Antagonist, MK-801

Andrea Szabó, Anita Lukács, and László Nagymajtényi

Department of Public Health, University of Szeged, Faculty of Medicine, Szeged, Hungary

Corresponding author: Andrea Szabó
    Department of Public Health
    University of Szeged Faculty of Medicine
    Dóm tér 10
    H-6720 Szeged, Hungary
    Telephone: +36-62-545-119
    Fax number: +36-62-545-120
    E-mail: szaboa@puhe.szote.u-szeged.hu

CEJOEM 2005, Vol.11. No.4.: 327–336

Key words:
3-nitropropionic acid, MK-801, acoustic startle response with prepulse inhibition, climbing time, evoked potentials, rat

Abstract:
3-nitripropionic acid (3-NP) can give rise to the pathological picture of neurodegenerative diseases associated with dementia (e.g., Huntington’s disease), but this effect can be counterbalanced by MK-801, an NMDA antagonist. In this study, male Wistar rats were used (4 groups, 10 rats per group). In the first group, a single intraperitoneal dose of 20 mg/kg 3-NP was administered, the second group was given a single dose of 0.4 mg/kg MK-801, i.p. The third group received MK-801 first and 30 minutes later 3-NP. The fourth (control) group was treated with saline. Neurobehavioral examinations (acoustic startle response with prepulse inhibition, climbing time) were done before the treatment and 24 h later. Electrophysiological investigations (evoked cortical and peripheral activity) were done 24 hours after the injection of the toxins. In the cortical evoked activity only somatosensory evoked potentials showed significant alterations: MK-801 increased their latency and decreased their duration, the combined treatment decreased the latency. The conduction velocity of action potentials – evoked by double pulses in the peripheral nerve – increased markedly after MK-801 and combination treatment. There were more noise-positive responses after 3-NP administration in the acoustic reflex following prepulse inhibition, while MK-801 and combination treatment remained unaffected by the level of prepulse inhibition. MK-801 relatively decreased, 3-NP relatively increased the climbing time, but in the combination group it returned near the level of the control group.
    The results obtained point to some protective effect of MK-801 in neurobehavioral experiments, but the findings of electrophysiological studies seem to be unequivocal.

Received: 5 December 2005
Accepted: 8 May 2006
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