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Dopamine Receptor D4 Polymorphism Predicts the Effect of L-DOPA on Gambling Behavior

(who knows if this little study has clinical significance. If it does, when we know the % of population in which this polymorphism occurs, may be able to determine the true incidence of gambling in PD pts who take L-DOPA meds)

Dopamine Receptor D4 Polymorphism Predicts the Effect of L-DOPA on Gambling Behavior
Biological Psychiatry, 12/07/09

The findings demonstrate that genetic variation in the DRD4 gene determines an individual's gambling behavior in response to a dopaminergic drug challenge. They may have implications for the treatment of Parkinson's disease patients by offering a genotype approach for determining individual susceptibilities for pathological gambling and may also afford insights into the vulnerability mechanisms underlying addictive behavior.

http://www.journals.elsevierhealth.c...11238/abstract

Dopamine Receptor D4 Polymorphism Predicts the Effect of L-DOPA on Gambling Behavior

Christoph Eiseneggera, Daria Knochb, Richard P. Ebsteinc, Lorena R.R. Gianottib, Peter S. Sándord, Ernst Fehrae

Background
There is ample evidence that a subgroup of Parkinson's disease patients who are treated with dopaminergic drugs develop certain behavioral addictions such as pathological gambling. The fact that only a subgroup of these patients develops pathological gambling suggests an interaction between dopaminergic drug treatment and individual susceptibility factors. These are potentially of genetic origin, since research in healthy subjects suggests that vulnerability for pathological gambling may be linked to variation in the dopamine receptor D4 (DRD4) gene. ...
Methods
We administered 300 mg of L-dihydroxyphenylalanine (L-DOPA) or placebo to 200 healthy male subjects who were all genotyped for their DRD4 polymorphism. Subjects played a gambling task 60 minutes after L-DOPA administration.

Results
Without considering genetic information, L-DOPA administration did not lead to an increase in gambling propensity compared with placebo. As expected, however, an individual's DRD4 polymorphism accounted for variation in gambling behavior after the administration of L-DOPA. Subjects who carry at least one copy of the 7-repeat allele showed an increased gambling propensity after dopaminergic stimulation.

Conclusions
These findings demonstrate that genetic variation in the DRD4 gene determines an individual's gambling behavior in response to a dopaminergic drug challenge...

Haven't left the forum....just a certain thread.

There's a lot of conflicting information out there. But it's all good because "Forewarned is forearmed"!

http://www.dana.org/news/Brainwork/detail.aspx?id=23406

Quote:

Recent studies of people with Parkinson’s suggest that newer and more powerful dopamine “agonists,” which bind to dopamine receptors on brain cells, are more likely to produce this “ventral overdose” effect. A review in Movement Disorders in 2007 found that pathological gambling behavior has been diagnosed two to eight times more frequently among Parkinson’s patients who take these agonists than among the general population. Yet it is not easy to reconcile such an effect with current models of dopamine signaling.

According to these models, the perception of an unexpected reward stimulus leads to a short-term burst of excitement among dopamine-producing neurons in the midbrain, near the brainstem. The brief episode of increased firing results in a quick but sizeable surge of dopamine along these neurons’ output fibers and into target regions in the striatum. In the ventral striatum, this dopamine surge is widely thought to be a primary learning signal, effectively telling the brain how much to value the relevant stimulus.

However, this signal is known to be mediated mainly by dopamine “D1” receptors on striatal neurons. And as Dagher points out, “dopamine agonists that are used clinically don’t act on the D1 receptor. They act only on dopamine D2 and D3 receptors.”

Quote:

How would dopamine agonists block the influence of these prefrontal areas and thereby impair reversal learning? According to one prominent hypothesis, based on work in rodents and published in 2005 in Nature Neuroscience, the influence of prefrontal signals on striatal neurons is regulated by striatal dopamine levels, via D2 receptors. “Dopamine can act as a traffic cop to decide which input has the most influence” over striatal neurons, Dagher says.

In this view, too much of a D2-agonist Parkinson’s medication would dial down the prefrontal influence, allowing behavior to become less restrained and less thoughtful. Understanding how this prefrontal-limbic balancing act can be disrupted is an area of intense research, Clark says.

dopamine agonists and gambling

If the results of this study obtain, forgot to state the obvious--pre testing for this polymorphism should enable individual medication prescribing so those with this SNP do not receive the dopamine agonists...

Don't tell me this!
quoting:
There is ample evidence that a subgroup of Parkinson's disease patients who are treated with dopaminergic drugs develop certain behavioral addictions such as pathological gambling. The fact that only a subgroup of these patients develops pathological gambling suggests an interaction between dopaminergic drug treatment and individual susceptibility factors. These are potentially of genetic origin, since research in healthy subjects suggests that vulnerability for pathological gambling may be linked to variation in the dopamine receptor D4 (DRD4) gene. ...
Methods

Take away my scratchers and agonists, but not my L-dopa! (I knew this all along) And we have alcoholics in our family - hmmmmm?

Peggy :eek:

23andme and polymorphism in DRD4 gene

Wondering if 23andme genetic profiling checks for this mutation, or if one could utilize the "browse raw data" feature and insert it into one's report? I will attempt to find an answer later; am overcommitted for the next few weeks. ANyone else know the answer? madelyn

you know what I think it boils down to? It's the reward and release of endorphines that are the causal agents in these situations.. If I am doing somet hing I reallly enjoy and am getting excited about (and before your mind wanders too far, let's say playing a pinball machine). When I am winning, then I am releasing endorphines and adrenaline, and what little dopamine I make, too. Thus, I want to continue with the behavior that is giving me such "pleasure."

PWP are needing their brains to be rewired (that's why the DBS surgey is so successful). We either over-react or under-react at stimuli.

Anyway, that's how I see it. Good idea, Olsen, about asking 23andme to check for a mutation.

Peggy

Post deleted. Data grossly misquoted.

:( If you read my post of last night, I apologize for the hash I made of the research.
Lesson learned: Beware of late-night posting on other's work without the data in hand.
Sorry.
Robert

I was impressed!
I wish I could make hash like that!
Peg