Role of dopaminergic treatment in dopamine receptor down-regulation in advanced Parkinson disease: a positron emission tomographic study.

Abstract

BACKGROUND:

In patients with advanced Parkinson disease (PD) who are undergoing long-term treatment with a dopaminergic medication, a down-regulation of striatal dopamine D2 receptor expression has been demonstrated and interpreted as a consequence of either the disease itself or dopaminergic drug administration.

OBJECTIVE:

To compare, using positron emission tomography, the striatal binding of raclopride carbon C 11, a dopamine D2 receptor ligand, in PD patients who completely discontinued dopaminergic therapy (off drug) with that in PD patients who continued receiving dopaminergic therapy (on drug) after undergoing subthalamic nucleus stimulation.

MAIN OUTCOME MEASURES:

The positron emission tomographic data were acquired in off-stimulation and, for 12 hours, off-medication conditions. Five off-drug PD patients, 7 on-drug PD patients, and 8 healthy subjects participated.

RESULTS:

In off-drug PD patients, the putaminal raclopride C 11 binding was 24% higher than in on-drug PD patients. The same tendency was noted for the caudate nucleus, but was not significant (P=.07). Compared with control subjects, the putaminal raclopride C 11 binding was increased by 21% in off-drug and was normal in on-drug PD patients. Compared with controls, the caudate raclopride C 11 binding was reduced by 23% in on-drug and was normal in off-drug PD patients. Further analysis using statistical parametric mapping showed a significant increase of binding bilaterally in the caudate nucleus and putamen in off-drug compared with on-drug PD patients (P=.002 at cluster level).

CONCLUSIONS:

The down-regulation of dopamine D2 receptors probably relates to the long-term and intermittent administration of dopaminergic treatments rather than to disease progression. This phenomenon is reversed by the complete withdrawal of dopaminergic drugs. Furthermore, an up-regulation of putaminal dopamine D2 receptors is demonstrated in late-stage PD after dopaminergic drug withdrawal.

• Authors: Stéphane Thobois, François Vingerhoets, Valerie Fraix, Jing Xie-Brustolin, Hélène Mollion, Nicolas Costes, Patrick Mertens, Alim-Louis Benabid, Pierre Pollak, Emmanuel Broussolle
• Journal: Archives of neurology (Arch Neurol) Vol. 61 Issue 11 Pg. 1705-9 (Nov 2004) ISSN: 0003-9942 [Print] United States
• PMID: 15534182 (Publication Type: Clinical Trial, Comparative Study, Journal Article)

Chemical References

• Dopamine Agents
• Dopamine Antagonists
• Ligands
• Receptors, Dopamine D2
• Raclopride

Topics

• Aged
• Disease Progression
• Dopamine Agents (pharmacology, therapeutic use)
• Dopamine Antagonists
• Down-Regulation
• Electric Stimulation Therapy
• Female
• Humans
• Ligands
• Male
• Middle Aged
• Parkinson Disease (drug therapy, physiopathology)
• Positron-Emission Tomography
• Raclopride
• Receptors, Dopamine D2 (biosynthesis, physiology)
• Subthalamic Nucleus (physiology)