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Temporal patterns of motor behavioural improvements by MK-801 in Mongolian gerbils submitted to different duration of
Branka Janać1, Vesna Selaković, Lidija Radenović
1Department of Neurophysiology, Institute for Biological Research, Bulevar Despota Stefana 142, 11000 Belgrade, Serbia. janac@ibiss.bg.ac.yu
Abstract:
The purpose of this study was to investigate the temporal pattern of NMDA receptors antagonist-MK-801 on motor behaviour parameters in gerbils submitted to different duration of global cerebral ischemia. The common carotid arteries of gerbils were occluded for 5, 10 or 15min. Gerbils were given MK-801 (3mg/kg i.p.) or saline immediately after the occlusion in normothermic conditions prior to testing. Motor activity was registered 1, 2, 4, 7, 14, 21 and 28 days after reperfusion during 60min by open field test. At the same time, the effect of NMDA receptor blockade was followed in vivo by monitoring the neurological status of whole animals or at the cellular level by standard light and confocal microscopy on brain slices. Post-ischemic gerbils quickly developed hypermotor response with the most intensity in animals submitted to 15min ischemia. MK-801 administrated immediately after ischemia significantly decreased this hyperactivity. In all ischemic-treated animals, behavioural suppression by MK-801 was observed already 1 day after occlusion and was lasting as far as observed ischemia-dependent hypermotor responses. Beneficial effect of MK-801 was also confirmed by morphological and neurological status data. These findings suggest that sustained ischemia-induced hyperactivity is related to abnormalities in NMDA glutamatergic function, as well as its manifestation could be completely abolished by NMDA receptor blockade immediately after ischemic insult.
Insights
MK-801, an NMDA receptor antagonist, significantly reduced hyperactivity in gerbils following global cerebral ischemia. This blockade, administered immediately after ischemia, abolished behavioral abnormalities and showed lasting beneficial effects.
Area of Science:
- Neuroscience
- Ischemia Research
- Pharmacology
Background:
- Global cerebral ischemia can lead to significant motor behavioral changes.
- NMDA receptors play a crucial role in neuronal function and excitotoxicity.
- Understanding the temporal effects of receptor antagonists post-ischemia is vital for therapeutic development.
Purpose of the Study:
- To investigate the temporal effects of the NMDA receptor antagonist MK-801 on motor behavior in gerbils after global cerebral ischemia of varying durations.
- To assess the impact of immediate post-ischemic MK-801 administration on neurological and cellular levels.
- To determine the relationship between NMDA receptor function and ischemia-induced hyperactivity.
Main Methods:
- Gerbils underwent carotid artery occlusion for 5, 10, or 15 minutes, followed by immediate administration of MK-801 (3mg/kg i.p.) or saline.
- Motor activity was assessed using the open field test at multiple time points (1, 2, 4, 7, 14, 21, 28 days) post-reperfusion.
- Neurological status and brain tissue morphology (light and confocal microscopy) were evaluated to correlate behavioral changes with physiological effects.
Main Results:
- Ischemic gerbils exhibited pronounced hyperactivity, most severe after 15 minutes of ischemia.
- MK-801 administration significantly suppressed post-ischemic hyperactivity, with effects observed as early as 1 day and persisting throughout the study duration.
- Beneficial effects of MK-801 were corroborated by improved neurological status and morphological data.
Conclusions:
- Sustained hyperactivity following global cerebral ischemia is linked to dysregulation of NMDA glutamatergic function.
- Immediate blockade of NMDA receptors with MK-801 can effectively abolish ischemia-induced hyperactivity.
- Early intervention with NMDA receptor antagonists holds therapeutic potential for mitigating behavioral deficits after ischemic insults.
