• Eur. J. Pharmacol. · Feb 2011

    Comparative Study

    Effects of AMPA and clomethiazole on spreading depression cycles in the rat neocortex in vivo.

    • Jonas I Addae, Nakisha Ali, and Trevor W Stone.
    • Faculty of Medical Sciences, University of the West Indies, St. Augustine, Trinidad and Tobago. Jonas.Addae@sta.uwi.edu
    • Eur. J. Pharmacol. 2011 Feb 25;653(1-3):41-6.

    AbstractIn hippocampal slices, inhibition of AMPA receptors unmasks synaptic transmission via NMDA receptors, suggesting that AMPA receptor activation normally inhibits synaptic transmission via NMDA receptors. Activation of NMDA receptors is involved in the pathogenesis of cortical spreading depression (CSD) which has been implicated in the pathogenesis of migraine aura and neuronal damage from peri-infarct depolarizations. In this study we examined whether NMDA receptor transmission could be unmasked in the neocortex in vivo by AMPA receptor blockage and whether AMPA receptors could affect CSD induced by 200 mM KCl. We further compared the effects of AMPA to those of the NMDA receptor antagonist, 2-amino-5-phosphono-pentanoic acid (2AP5), and the GABA-mimetic drug clomethiazole. The NMDA receptor antagonist MK-801 did not affect the baseline somatosensory evoked potentials (SEPs). In a medium with no Mg(2+), the AMPA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) caused marked reduction in the SEP size which subsequently recovered partially; MK-801 blocked these partially recovered SEPs. AMPA (50 μM but not at 5 μM or 250 μM) and 2AP5 (10 μM) significantly reduced the number of CSD cycles. The effect of AMPA was not changed by co-applying it with cyclothiazide, which blocks AMPA receptor desensitization. Clomethiazole (100 mg/kg i.p.) did not significantly affect the number of CSD cycles. Only 2AP5 significantly reduced the potentiation that follows CSD. We conclude that activation of AMPA receptors can suppress the actions of NMDA receptors in the neocortex; this could be an intrinsic protective mechanism against CSD and also provide a possible therapeutic strategy against CSD-related neurological conditions.Copyright © 2010 Elsevier B.V. All rights reserved.

      Pubmed     Full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…