Levodopa and pramipexole effects on presynaptic dopamine PET markers and estimated dopamine release

  • Vesna Sossi
  • Katherine Dinelle
  • Michael Schulzer
  • Edwin Mak
  • Doris J. Doudet
  • Raúl de la Fuente-Fernández
Original Article

Abstract

Purpose

Levodopa and dopamine (DA) agonist therapy are two common treatments for Parkinson’s disease (PD). There is controversy about the effects of these treatments on disease progression and imaging markers. Here we used multi-tracer positron emission tomography imaging and a unilateral 6-hydroxydopamine (6-OHDA) rat model of PD to evaluate in vivo the effects of chronic levodopa and pramipexole treatments on measurements of vesicular monoamine transporter type 2 (VMAT2), dopamine transporter (DAT) levels, and on levodopa-induced changes in synaptic DA levels [Δ(DA)].

Methods

Twenty-three unilaterally 6-OHDA lesioned rats underwent an 11C-dihydrotetrabenazine (DTBZ, VMAT2 marker), an 11C-methylphenidate (MP, DAT marker), and a double 11C-raclopride (RAC, D2-type receptor marker) scan. They were assigned to three treatment groups: saline (N = 7), pramipexole (N = 8), and levodopa (N = 8). After 4 weeks of treatment, imaging was repeated.

Results

Results showed (1) a significant treatment effect on DTBZ, with pramipexole decreasing DTBZ binding compared to levodopa, (2) significant side and treatment-striatal side interaction effects for MP, indicating that levodopa tends to decrease MP binding compared to pramipexole, and (3) no treatment effect on Δ(DA).

Conclusion

These data indicate that while chronic dopaminergic pharmacological treatment affects DTBZ and MP binding, it does not affect levodopa-induced changes in synaptic DA level.

Keywords

DAT Dopamine agonist Levodopa 6-OHDA rodent model Parkinson’s disease VMAT2 

Notes

Acknowledgements

This work was supported by CIHR, NSERC, MSFHR and Triumf Life Science.

Conflicts of interest

None.

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Vesna Sossi
    • 1
    • 2
  • Katherine Dinelle
    • 1
  • Michael Schulzer
    • 2
  • Edwin Mak
    • 2
  • Doris J. Doudet
    • 1
  • Raúl de la Fuente-Fernández
    • 1
    • 2
  1. 1.University of British ColumbiaVancouverCanada
  2. 2.Department of Physics and AstronomyVancouverCanada

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