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Re: Mood Stablizer with ZERO serotonin effect? » linkadge

Posted by SLS on June 10, 2008, at 11:10:29

In reply to Re: Mood Stablizer with ZERO serotonin effect?, posted by linkadge on June 10, 2008, at 7:32:40

> >This in turn increases dopamine release in the >nucleus accumbens, the reward, pleasure, and >motivational center in the limbic system

> Is this true?

I don't know for sure. The theory is uniquely mine. My conclusion is based on:

1. Lamotrigine reduces glutamate release in the thalamus.

2. Thalamic glutamatergic pathways leading to the nucleus accumbens are muted.

3. The function of these pathways is to inhibit dopamine release in the nucleus accumbens.

4. Reduced firings of these glutamatergic pathways disinhibits dopamine release in the nucleus accumbens, thereby increasing dopaminergic activity there.

> The only reason I ask is because lamotrigine has dopamine depleting activity in certain brain regions.

I can see that the article concerns itself more with the basal ganglia and striatum than with the thalamus or nucleus accumbens.

From the article:

"In support of conclusions regarding our patient, lamotrigine exerted prodystonic effects in Syrian hamsters with primary generalized dystonia"

I wonder whether such effects would be expressed had the hamsters not had dystonia in the first place. I really don't know where else the anti-glutamatergic properties of lamotrigine are exerted. Perhaps it is the sodium channel antagonism that produces the dystonia. It would be interesting to look at a brain map with detailed circuitry to determine the interaction between GLU, GABA, and DA. It sounds like a lot of work, though.

Would the vulnerability to lamotrigine-induced dystonia be greater in epileptics than in non-epileptics? How about people previously exposed to neuroleptics? I have very little reason to think this, but if lamotrigine can directly enhance DAergic neurotransmission in other structures of the brain, perhaps upregulated postsynaptic receptors are overly sensitive to any increase in DAergic activation induced by lamotrigine.


- Scott

 

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