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L-DOPA Side Effects May Be Controllable

Rodent studies show 5-HT1B receptor agonist may inhibit abnormal effects of L-DOPA

THURSDAY, Feb. 7 (HealthDay News) -- While long-term treatment of Parkinson's disease with L-DOPA may lead to abnormal behaviors and movements, the use of 5-HT1B receptor agonists may provide an alternative approach in managing these adverse effects, according to research published online Feb. 6 in the Proceedings of the National Academy of Sciences Early Edition.

Xiaoqun Zhang, from the Rockefeller University in New York City, and colleagues carried out a series of experiments on mice and rat models of Parkinson's disease. Brains were lesioned in the median forebrain bundle of the right hemisphere using the neurotoxin, 6-hydroxydopamine (6-OHDA). Animals were treated with saline or L-DOPA and brains were examined for 5-HT1B receptors and presence of p11.

The researchers found that chronic L-DOPA administration resulted in increased levels of 5-HT1B receptors and p11. Further, administration of the selective 5-HT1B receptor agonist, CP94253, resulted in an inhibition of abnormal rotational behavior and involuntary movements, stimulated via a serotonergic pathway. The researchers hypothesize that the serotonergic pathway can be suppressed pharmacologically.

Zhang and colleagues conclude, "Because the blockade of D1Rs [dopamine D1 receptors] is not a treatment option for L-DOPA-induced side effects and because it would diminish the therapeutic efficacy of L-DOPA, the use of 5-HT1B receptor agonists to modulate signaling in striatonigral neurons may offer an alternative approach."

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