Dopamine Deficiency or Dopamine sensitive neuron deficiency? 
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 Dopamine Deficiency or Dopamine sensitive neuron deficiency?


> Hi,

> Consider the following case:

> A patient has lost all his motivation and feelings and is suffering from
> major depression. He has a little parkinsonism, in that he has a little
> tremor in his fingers.

What type of tremor? Resting or action tremor? You need more than that
to get a diagnosis of Parkinson's disease. What about other parkinsonian
signs? Masked facies, cogwheel rigidity, shuffling gait, positive
glabellar tap, etc.

> He is treated with Bromocriptine (Parlodel, 1 tablet daily) and a Dompamine
> antagonist (Seroquel, 100mg). His tremors go away, but his depression and
> lack of motivation and lack of feelings remain. (He is treated with
> Fluoxetine too, which does not work).

Seroquel has minimal dopamine blocking (ie antagonist) effects. A good
choice for a parkinsonian patient with psychosis. However, you do not
mention that he is psychotic (delusional, hallucinations etc). If he is
not psychotic, what is the rationale of using Seroquel?

> So, how can I distinguish between a dopamine deficiency from a dopamine
> sensitive neuron deficiency? (In other words, there could have been a
> desensitization of dopamine sensitive neurons through extreme stress).

What evidence is there that extreme stress would have this effect. I am
not aware that this can happen. I don't understand your concept of "a
dopamine sensitive neuron deficiency". What do you mean by that?

> Should some other dopamine agonist be used here?

It sounds like getting the antidepressant right might be the way to go.
However, there is not enough clinical information presented here to
offer a meaningful opinion.

Larry Brash

Thu, 02 Sep 2004 06:20:27 GMT
 Dopamine Deficiency or Dopamine sensitive neuron deficiency?
I think you are talking about the up regulation and down regulation of
neuronal receptors.  Up regulation can be due to either one an increase in
receptors or from an increased sensitivity of receptors, this can happen
after a receptor has been reversibly blocked for some period of time, and
the response then to stimulation is magnified after the blockade is removed.
Let me give an example in a different system.  A child has an ear infection,
and has been unable to hear normally due to the infection's effect on
neuronal transmission and alteration of pressure which allows the sound to
be heard.  The child then undergoes surgery to remove the infection, drain
the ear, and re-establish a healthy inner and middle ear.  The first sounds
he/she hears will be amplified, probably exceptionally loud.  Question on
this one is this a receptor number effect, or a receptor sensitivity effect.
(are the two effects one and the same).    Actually there is an enormous
body of literature on these subjects and the subject of dopamine receptors.

Fri, 03 Sep 2004 14:08:50 GMT
 Dopamine Deficiency or Dopamine sensitive neuron deficiency?


> > So, Seroquel would help as a long term treatment by an antagonist has an
> > effect which makes the brain produce more dopamine sensitive neurons.
> > Maybe this is just an assumption.

> for what its worth, seroquel (i'm pretty sure) falls into a category
> of antipsychotics commonly called "neuroleptics".

No, it is an atypical antipsychotic. Neuroleptic means a drug that
causes extra-pyramidal side-effects, like the typical antipsychotics.
Seroquel does not cause these effects.

> unfortunately, these
> dopamine antagonists don't trick the brain into making more dopamine
> sensitive neurons- quite the opposite. a complication of long term
> neuroleptic use known as "malignant neuroleptic syndrome" (you can
> plug that into google)

No, again. Neuroleptic malignant syndrome (NMS) - the correct term - is
an ACUTE side-effect of ACUTE (usually) neuroleptic use. Are you getting
it confused with tardive dyskinesia (TD), which is a side-effect of long
term neuroleptics? The postulated mechanism of TD is that prolonged
dopamine blockade leads to denervation hypersensitivity or dopamine
receptor up-regulation.

> actually seems to decrease the number of
> functional dopamine receptors (or else decrease the CNS availability
> of dopamine). as a result, people actually get parkinsonian type
> symptoms- muscular rigidity, altered mental status &c.

Yes, you are describing neuroleptic malignant syndrome. It is a fairly
rare idiopathic reaction to neuroleptics. The causative  mechanism is
unknown. It is tempting to blame dopamine depletion, but unproven.

Larry Brash

Sun, 05 Sep 2004 18:49:54 GMT
 [ 3 post ] 

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