Subthalamotomy-induced changes in dopamine receptors in parkinsonian monkeys

Jourdain, Vincent A.; Morin, Nicolas; Morissette, Marc; Grégoire, Laurent; Paolo, Thérèse Di

doi:10.1016/j.expneurol.2014.08.018

Experimental Neurology

2014

DOI: 10.1016/j.expneurol.2014.08.018

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Subthalamotomy-induced changes in dopamine receptors in parkinsonian monkeys

Vincent A. Jourdain

Nicolas Morin

Marc Morissette

et al.

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Cited by 2 publications

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“…We observed a reversal of the levodopa-induced decreases in D 1 receptor-specific binding ipsilateral to the subthalamotomy and no effects on the D 2 -related system. 30 A reduction of STN glutamatergic activity had beneficial effects on PD symptoms, as predicted by the direct and indirect pathways model of the basal ganglia. 19 Given the glutamatergic nature of the STN, subthalamotomy is hypothesized to induce changes in levels of glutamate receptors in the basal ganglia through direct STN projections 60 or through a normalization of cortico-and thalamostriatal pathways.…”

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Changes in glutamate receptors in dyskinetic parkinsonian monkeys after unilateral subthalamotomy

Jourdain

Morin

Grégoire

et al. 2015

JNS

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abbreviatioNs AMPA = α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; GP = globus pallidus; GPe = GP externus; GPi = GP internus; LID = levodopa-induced dyskinesia; mGlu = metabotropic glutamate; MPTP = 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; NMDA = N-methyl-d-aspartate; PD = Parkinson disease; STN = subthalamic nucleus; 6-OHDA = 6-hydroxydopamine. obJect Unilateral subthalamotomy is a surgical procedure that may be used to alleviate disabling levodopa-induced dyskinesias (LIDs) in patients with Parkinson disease (PD). However, the mechanisms involved in LID remain largely unknown. The subthalamic nucleus (STN) is the sole glutamatergic nucleus within the basal ganglia, and its lesion may produce changes in glutamate receptors in various areas of the basal ganglia. The authors aimed to investigate the biochemical changes in glutamate receptors in striatal and pallidal regions of the basal ganglia after lesion of the STN in parkinsonian macaque monkeys. methods The authors treated 12 female ovariectomized monkeys with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD-like symptoms, treated 8 of these animals with 3,4-dihydroxy-l-phenylalanine (L-DOPA; levodopa) to induce LID, and performed unilateral subthalamotomy in 4 of these 8 monkeys. Four additional monkeys were treated with saline only and were used as controls. The MPTP monkeys had previously been shown to respond behaviorally to lower doses of levodopa after the STN lesion. Autoradiography of slices from postmortem brain tissues was used to visualize changes in the specific binding of striatal and pallidal ionotropic glutamate receptors (that is, of the α-amino-3-hydroxy 5-methyl-4-isoxazole propionate [AMPA] and N-methyl-d-aspartate [NMDA] NR1/NR2B subunit receptors) and of metabotropic glutamate (mGlu) receptors (that is, mGlu2/3 and mGlu5 receptors). The specific binding and distribution of glutamate receptors in the basal ganglia of the levodopa-treated, STN-lesioned MPTP monkeys were compared with those in the saline-treated control monkeys and in the saline-treated and levodopa-treated MPTP monkeys. results The autoradiographic results indicated that none of the pharmacological and surgical treatments produced changes in the specific binding of AMPA receptors in the basal ganglia. Levodopa treatment increased the specific binding of NMDA receptors in the basal ganglia. Subthalamotomy reversed these increases in the striatum, but in the globus pallidus (GP), the subthalamotomy reversed these increases only contralaterally. Levodopa treatment reversed MPTPinduced increases in mGlu2/3 receptors only in the GP. mGlu2/3 receptor-specific binding in the striatum and GP decreased bilaterally in the levodopa-treated, STN-lesioned MPTP monkeys compared with the other 3 groups. Compared with mGlu5 receptor-specific binding in the control monkeys, that of the levodopa-treated MPTP monkeys increased in the dorsal putamen and remained unchanged in the caudate nucleus and in the GP. coNclusioNs These results implicate glutamate recepto...

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Changes in glutamate receptors in dyskinetic parkinsonian monkeys after unilateral subthalamotomy

Jourdain

Morin

Grégoire

et al. 2015

JNS

Self Cite

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A quantitative approach to developing Parkinsonian monkeys ( Macaca fascicularis ) with intracerebroventricular 1-methyl-4-phenylpyridinium injections

Huang

et al. 2015

Journal of Neuroscience Methods

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Subthalamotomy-induced changes in dopamine receptors in parkinsonian monkeys

Cited by 2 publications

References 71 publications

Changes in glutamate receptors in dyskinetic parkinsonian monkeys after unilateral subthalamotomy

Changes in glutamate receptors in dyskinetic parkinsonian monkeys after unilateral subthalamotomy

A quantitative approach to developing Parkinsonian monkeys ( Macaca fascicularis ) with intracerebroventricular 1-methyl-4-phenylpyridinium injections

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