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Re: 5-ht2a and nmda » SLS

Posted by JohnX2 on March 24, 2002, at 2:54:41

In reply to Re: ltp in the hippocampus » JohnX2, posted by SLS on March 23, 2002, at 8:55:19


>
> In another post, you mentioned something regarding 5-HT2 receptors being somehow linked to NMDA function. Can you elaborate?
>
> Thanks.

I had this thought regarding SSRI poopout, amphetamine poopout, and NMDA antagonists. I don't have the details on hand, but I found a quick abstract confirming the link. If my memory serves me correct, the 5-ht2a receptors serve to depolarize (decrease the voltage threshold required to fire) the NMDA receptors somehow (directly or indirectly). Take this with a grain of salt.

John


Serotonin 5-HT2 receptor activation potentiates N-methyl-D-aspartate receptor-mediated ion currents by a protein kinase C-dependent mechanism.
J Neurosci Res 1996 Jul 15;45(2):153-60 (ISSN: 0360-4012)
Blank T; Zwart R; Nijholt I; Spiess J
Department of Molecular Neuroendocrinology, Max Planck Institute for Experimental Medicine, Gottingen, Germany.
Modulation of N-methyl-D-aspartate (NMDA) receptor-mediated ion currents by serotonin was investigated with a two-electrode voltage clamp technique in Xenopus oocytes injected with rat brain RNA. After a 1-min application of 200 nM serotonin a transient potentiation of the NMDA receptor-mediated ion currents was observed. The serotonin-induced enhancement was mimicked by the protein kinase C activators 1-oleoyl-2-acetyl-sn-glycerol (100 microM) and phorbol 12-myristate 13-acetate (10 nM), whereas the inactive phorbol ester 4-alpha-phorbol 12-myristate 13-acetate (10 nM) had no effect. From these observations it was concluded that protein kinase C was involved in the enhancement of NMDA-induced currents. In agreement with this conclusion, it was found that the serotonin effect was inhibited by the protein kinase C inhibitors sphingosine (1 microM) or staurosporine (1 microM) added 20 min before NMDA application and by oocyte injection of protein kinase C (PKC)-inhibitor peptide (500 ng/oocyte) 1 hr prior to recordings. The serotonin receptor involved was identified as a 5-HT2 receptor subtype by the finding that 200 nM of the selective 5-HT2 receptor agonist alpha-methyl-5-hydroxytryptamine mimicked the potentiation of NMDA-induced ion currents by serotonin. Furthermore, the observed potentiation was significantly reduced by co-application of serotonin with 100 microM of the selective 5-HT2 receptor antagonist ketanserin. These results indicate that 5-HT2 receptors enhance NMDA receptor function via phosphoinositol hydrolysis and subsequent stimulation of PKC.


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URL: http://www.dr-bob.org/babble/20020322/msgs/99794.html