Assessing nigrostriatal dysfunctions by pharmacological MRI in parkinsonian rhesus macaques

Zhiming Zhang, Anders H. Andersen, Yi Ai, Aaron Loveland, Peter A. Hardy, Greg A. Gerhardt, Don M. Gash

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


New imaging techniques are needed to longitudinally monitor the development, progression and treatment of Parkinson's disease. The present study was designed to test whether the blood oxygenation level-dependent (BOLD) response to dopaminergic stimulation as measured by pharmacological MRI (phMRI) correlated to specific histological and behavioral features of the parkinsonian state. Nine adult rhesus monkeys were rendered hemiparkinsonian by intracarotid administration of MPTP. Three months after MPTP treatment, the trained, MRI-adapted awake animals were scanned with a phMRI technique while being administered a presynaptic (d-amphetamine) or postsynaptic (apomorphine) dopamine stimulating agents. The primary findings were (1) the putamen and substantia nigra (SN) but not the caudate nucleus displayed significant BOLD responses to these dopaminergic drugs; (2) a significant relationship was found between amphetamine-evoked activation and the number of surviving dopamine neurons in the SN, which was also correlated with bradykinesia; and (3) inverse relationships were seen in response to apomorphine and amphetamine stimulation between the MPTP-lesioned and unlesioned putamen and SN. The results suggest that phMRI may prove useful for longitudinally monitoring the progression and treatment of PD.

Original languageEnglish
Pages (from-to)636-643
Number of pages8
Issue number2
StatePublished - Nov 1 2006

Bibliographical note

Funding Information:
This study was supported by grants from NIH: AG 13494 (DMG), NS39787, (GAG) and MH01245, (GAG).


  • Amphetamine
  • Apomorphine
  • MPTP
  • Parkinson's disease
  • Rhesus macaque
  • phMRI

ASJC Scopus subject areas

  • Neurology
  • Cognitive Neuroscience


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