[Comp-neuro] AM 404 and L-AP4 effects on the hippocampal mossy fiber synaptic transmission

[Sudhir Sivakumaran]

Hello everyone,

Does anyone have an idea about how AM404, an endocannabinoid uptake 
blocker, works in modulating release of neurotransmitter from the 
presynaptic neuron?

I mean, in our set of experiments, after using this drug, to confirm the 
presynaptic fiber as mossy fiber of the hippocampus, we use L-AP4, a 
mGluR agonist, which usually reduces transmission from the mossy fiber. 
But in the current experiments we are doing, L-AP4 doesn't seem to have 
any effect (or either we are catching the interneurons more often than 
usual!!!). So, I am wondering if it's possible that the accumulation of 
endocannabinoid (as a result of the uptake block) is in some way 
interfering with the effect of L-AP4? Is it possible that endocannbinoid 
in the synaptic cleft could somehow nullify the effect of this mGluR 
agonist?

Thanks to all in advance.

Best,
Sudhir