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GABAergics effects on LTP

narutokun

narutokun

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Aug 21, 2007
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Keeping it simple, is there any conclusive evidence that the chronic use of GABAergics can have negative effects on long term potentiation process? I've been noticing a decrease in the time needed for me to remember things as well as forgeting many things that have taken event on the past and that on normal conditions I wouldn't forget.
 
Any 2'-chloro or 2'-fluoro substituted benzodiazepines (clonazepam, lorazepam, midazolam, flunitrazepam etc) cause amnesia while you are on them, most likely they have high affinity for the alpha1 subtype of the GABA-A receptor which is associated with amnesia. Selective alpha1 agonists like zopiclone and zolpidem are even more amnestic still.

I'm not aware of GABA agonists having any long term effect on memory after an extended period of abstinence, although of course some drugs of this type such as alcohol are known to be neurotoxic, and similar allegations have been made in regards to the nitro-substituted benzodiazepines such as clonazepam and flunitrazepam, so it is possible that heavy use of these drugs might cause some lasting memory deficit.
 
^Indeed they have higher affinity for α1 receptors but from experience I disagree that any Z drugs are more amnesic than midazolam in specific. Even in suposedly equivalent doses I've noticed that midazolam causes much more profound anterograde amnesia than any Z drug.
 
Oh yeah thats true, but midazolam is known for being particularly amnestic.

I haven't tried midazolam myself, but I certainly thought that zopiclone is much more amnestic than either clonazepam or flunitrazepam, while zolpidem is probably about the same as far as amnesia goes (not nearly as fun though!)
 
weird, I never found zopiclone to be too amnesic. I've lost far more days to benzos than any z-drug
 
I found zopiclone and midazolam to be equivalent in their capacity to cause amnesia. Really bad idea to take either and then put things in a "safe place" :/
 
This is not scientific, I know, but I still feel some deficit in short-term memory after abusing barbital for a while (I can't remember how long, but I went through about 30g of the stuff :/) that was about two years ago.

Things I tend to do automatically, I can't remember well, and my ability to focus on a task has diminished to the point of me feeling like I have a touch of ADD, while I can remember doing tasks I need to focus on (and manage to focus on successfully) I can't usually remember what I had for dinner last night.
 
^Even before benzos it was already hard for me to remember what I ate at a previous night's dinner lol.
 
I get the impression that you misinterpret the whole concept of LTP/LTD. Although unltimately this does affect memory and learning, it in itself is more of a micro-scale process in neuronal signalling that cannot be generalized to an outward behavioural/cognitive change.

To my knowledge, LTP deals with the electrochemical signalling between certain neurons, and admittedly my knowledge of these things seriously dwindles when it comes to electrophysiology.

For what its worth, I encountered the idea mostly when reading about NMDA-antagonists, which supposedly increase long-term potentiation (the implication of which I am not informed enought to comment on.)
 
^Huh? 8( I don't understand what you mean by this:
cannot be generalized to an outward behavioural/cognitive change.
Click to expand...
If it got too blurry just forget the whole LTP theory shit and rename the thread to something like "GABAergics effects on memory".
 
Well you probably don't understand it for the same reason I don't understand it completely: we are both not neuropharmacologists. The process of Long Term Potentiation had absolutely no meaning to me the first time I read about it because it deals a lot with neurotransmission at an electric level.
 
Remember we're talking long term potentiation here (think neural/synaptic plasticity).



Here's a study which promotes neural inhibition as beneficial to cognition.


Cerebral Cortex 2005 15(7):921-928; doi:10.1093/cercor/bhh191


Nootropic Agents Enhance the Recruitment of Fast GABAA Inhibition in Rat Neocortex

Douglas S.F. Ling1 and Larry S. Benardo1,2 ]
1 Department of Physiology and Pharmacology, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA and 2 Department of Neurology, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA


It is widely believed that nootropic (cognition-enhancing) agents produce their therapeutic effects by augmenting excitatory synaptic transmission in cortical circuits, primarily through positive modulation of -amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors (AMPARs). However, GABA-mediated inhibition is also critical for cognition, and enhanced GABA function may be likewise therapeutic for cognitive disorders. Could nootropics act through such a mechanism as well? To address this question, we examined the effects of nootropic agents on excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) recorded from layer V pyramidal cells in acute slices of somatosensory cortex. Aniracetam, a positive modulator of AMPA/kainate receptors, increased the peak amplitude of evoked EPSCs and the amplitude and duration of polysynaptic fast IPSCs, manifested as a greater total charge carried by IPSCs. As a result, the EPSC/IPSC ratio of total charge was decreased, representing a shift in the excitation–inhibition balance that favors inhibition. Aniracetam did not affect the magnitude of either monosynaptic IPSCs (mono-IPSCs) recorded in the presence of excitatory amino acid receptor antagonists, or miniature IPSCs (mIPSCs) recorded in the presence of tetrodotoxin. However, the duration of both mono-IPSCs and mIPSCs was prolonged, suggesting that aniracetam also directly modulates GABAergic transmission. Cyclothiazide, a preferential modulator of AMPAR function, enhanced the magnitude and duration of polysynaptic IPSCs, similar to aniracetam, but did not affect mono-IPSCs. Concanavalin A, a kainate receptor modulator, had little effect on EPSCs or IPSCs, suggesting there was no contribution from kainate receptor activity. These findings indicate that AMPAR modulators strengthen inhibition in neocortical pyramidal cells, most likely by altering the kinetics of AMPARs on synaptically connected interneurons and possibly by modulating GABAA receptor responses in pyramidal cells. This suggests that the therapeutic actions of nootropic agents may be partly mediated through enhanced cortical GABAergic inhibition, and not solely through the direct modification of excitation, as previously thought.

http://cercor.oxfordjournals.org/cgi/conte...stract/15/7/921



Bluelight really needs more journal sourcing :P
 
^I've been taking piracetam for a few years due to the fact that I can't get any other racetams here where I live. I hear that aniracetam is more potent than piracetam, does anyone know how many times more potent? Oh well. :\
 
They say around 10, though it's completely different & not really up for comparison (smooth anxiolytic action, doesn't really work for me whereas piracteam & oxiracetam do).
 
cannot be generalized to an outward behavioural/cognitive change.
Click to expand...

Changes in neurotransmitters in regards to LTP won't neccesairly have external effects; ie. you won't have a different personality, act differently, have a changed experiential view of the wordl, I think is what Jamshyd is saying.
 
Hmmmm...


Greater capabilities I would have thought. Playing the piano better, remembering a book, whistling a tune (all require the act itself, or learning).
 
How about this: can you explain the process of Long Term Potentiation as you understand it? Maybe that will help people here reply to your questions.
 
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