Posted by SLS on August 31, 2014, at 14:49:43
In reply to 4 weeks of deep tms... » johnLA, posted by johnLA on August 31, 2014, at 9:42:36
> if anybody has anything to say about lamictal, besides the rash, please let me know. i am curious what it might be able to do for me.
I came up with a silly idea a number of years ago.
I read that certain glutamate pathways efferent from the thalamus and hippocampus actually inhibited dopamine activity in mesolimbic structures, namely, the nucleus accumbens and the ventral tegmental area. Lamictal reduces glutamate release in both the thalamus and hippocampus, and might therefore act to disinhibit dopamine neurons and increase dopamine release in the nucleus accumbens and ventral tegmental area, regions that participate in reward and mood. I just want to mention that other glutamate pathways act to stimulate dopamine release. That's why it is often better to conceptualize the brain as a network of wires rather than a bucket of chemicals. Where a neuron is routed is at least as important as which neurotransmitter it uses to transduce the message it carries. Remember, the same receptor can be excitatory or inhibitory depending on its location along the cell membrane.
One line of reasoning:
1. There are glutamate neurons arising from the thalamus and hippocampus.
2. These glutamate neurons are routed to two mesolimbic structures that are important for the experience of reward and good mood.
3. The neurons in the mesolimibic structures that are responsible for reward and good mood are driven by dopamine.
3. When the glutamate neurons from the thalamus and hypothalamus are innervated (activated), they inhibit (reduce) the firing rate of the dopamine neurons in the mesolimbic structures.
4. Too much glutamate leads to too little dopamine in this case.
5. Lamotrigine (Lamictal) inhibits the release of glutamate from neurons located in the thalamus and hippocampus. The firing rate of glutamate neurons is therefore reduced. Less glutamate leads to more dopamine.
* This kind of functional relationshop is known as disinhibition.
6. By disinhibiting dopamine neurons via the inhibition of glutamate release by lamotrigine, people may experience an improvement in the severity of their depression as the activity in the nucleus accumbens and ventral tegmental area is increased.
7. Since the ventral tegmental area innervates the prefrontal cortex, it may be that lamotrigine yields an increase in activity here, too. If so, one might expect an improvement in some other aspects of mood and cognitive function. Unfortunately, lamotrigine also blocks sodium channels. The cognitive and memory impairments this produces usually obscures any enhancement in prefrontal cortical activity. There may be other mechanisms that contribute to these cognitive side effects. I haven't looked into it.
- ScottSome see things as they are and ask why.
I dream of things that never were and ask why not.- George Bernard Shaw
poster:SLS
thread:1069147
URL: http://www.dr-bob.org/babble/20140815/msgs/1070580.html