Animal Tranqulizer Ketamine can stop your depression: This is how.

I wanted to quickly summarize a ground breaking change in perspective going on in psychiatry, the field of treating mental illness. There is a new realization that glutamate dysfunction is behind a wide range of mental illnesses. Especially major depressive disorder and suicide. This realization has profound consequences, and many new and promising drug trails are ongoing. One of the more famous drugs is ketamine, which is a drug known as anesthetic (ie used during surgery to put and keep animals and humans asleep). Now, small doses of ketamine are being used in controlled trials to help solders with severe PTSD and depression overcome the intense anxieties. And strangely enough, this seems to all come down to synaptogensis and neural plasticity. 

Recall that glutamate has two types of receptors. AMPA  which causes small depolarizations of the cell. Lots of AMPA receptors need to open in order for a neuron to fire.  However, once the neuron fires (and glutamate is present), NMDA receptors also fire. This lets in a large influx of calcium, that among other things, is necessary for synaptic plasticity. For an overview of AMPA and NMDA see here and here.  The key take away is that calcium levels are critical for long term potentiation (LTP) and long term depression (LTD).

 
This makes NMDA critical for maintaining the number and strength of synapses in the dendritic tree. Too much NMDA or too little NMDA, will cause disruptions in synaptic strength as well as  synaptic layout. While which brain regions are affected changes from disorder to disorder, disruptions  in synaptogenisis has been seen in PTSD, anxiety, major depressive disorder, bipolar disorder, schizophrenia, and autism. Specifically, all of these disorders seem to have one thing in common, excessive synaptic pruning. That is there are less synapses than one would expect.

That is where ketamine comes to the rescue. Ketamine is an NMDA antagonist, meaning that it blocks the NMDA receptor. This causes a huge drop in the calcium influx to the cell, and signals it to grow many new synapses. This synaptogenesis literally rewires the brain in a single dosage of ketamine. Couple that with therapy while the ketamine is being administered, and the doctor can alleviate a patients depression in a single treatment session. As stated, this has so far been tested in solders with PTSD with amazingly encouraging results thus far.

This is a great topic for any budding neuroscientist to get into. There is still a lot of work to be done on glutamate, including figuring out exactly how synpatogenesis effects mood, and how all these disorders relate to the receptor. Plus, there are probably many more compounds that can be designed to effect NMDA receptors in the brain, and potentially treat the other disorders beyond just PTSD
 
For a great 1 hour summary of these results, you can watch  Dr. Rakesh Jain discuss the recent progress with NMDA and ketamine. It is well worth the watch: 
https://www.youtube.com/watch?v=E6Ft4a0F0ZU&t=13s

Author: Alexander J. White