Increased slow oscillatory activity in substantia nigra pars reticulata triggers abnormal involuntary movements in the 6-OHDA-lesioned rat in the presence of excessive extracelullar striatal dopamine

Meissner, Wassilios G.; Ravenscroft, Paula; Reese, René; Harnack, Daniel; Morgenstern, Rudolf; Kupsch, Andreas; Klitgaard, Henrik; Bioulac, Bernard; Gross, Christian E.; Bézard, Erwan; Boraud, Thomas

doi:10.1016/j.nbd.2006.01.009

Cited by 139 publications

(113 citation statements)

References 49 publications

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“…A primary involvement of D1 receptors and the direct basal ganglia pathway is suggested by other recent studies too (Aubert et al, 2005;Fiorentini et al, 2006), and by the fact that D2 family agonists are less likely to induce dyskinesia in patients and animal models of PD than unselective and D1/D5 selective agonists (present findings; Gnanalingham et al, 1995;Blanchet et al, 1996;Pearce et al, 1999;Goulet and Madras, 2000;Nutt, 2000;Rascol et al, 2001;Lundblad et al, 2002;Monville et al, 2005). A recent study established that levodopa-induced dyskinesia in the rat 6-OHDA model is related to increased synchronization of afferent activity to the basal ganglia output nuclei (Meissner et al, 2006). Our present findings suggest that D1 receptor mediated over-activation of a sensitized direct pathway may contribute to driving this abnormal low frequency synchronization in the basal ganglia output nuclei and levodopa-induced dyskinesia.…”

Section: Severity Of Fd Is Related To Striatal and Motor Cortex Bold supporting

confidence: 68%

Mapping the Effects of Three Dopamine Agonists with Different Dyskinetogenic Potential and Receptor Selectivity Using Pharmacological Functional Magnetic Resonance Imaging

Delfino

Kalisch

Czisch

et al. 2007

Neuropsychopharmacol

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The mechanisms underlying dopamine agonist-induced dyskinesia in Parkinson's disease remain poorly understood. Similar to patients, rats with severe nigrostriatal degeneration induced by 6-hydroxydopamine are more likely to show dyskinesia during chronic treatment with unselective dopamine receptor agonists than with D2 agonists, suggesting that D1 receptor stimulation alone or in conjunction with D2 receptor stimulation increases the chances of experiencing dyskinesia. As a first step towards disclosing drug-induced brain activation in dyskinesia, we examined the effects of dopamine agonists on behavior and blood oxygenation level-dependent (BOLD) signal in the striatum and motor cortex of rats with unilateral nigrostriatal lesions. Rats were rendered dyskinetic before pharmacologic functional magnetic resonance imaging by means of a repeated treatment regime with dopamine agonists. The unselective agonist apomorphine and the selective D1/D5 agonist SKF-81297 induced strong forelimb dyskinesia (FD) and axial dystonia and increased BOLD signal in the denervated striatum. Besides, SKF-81297 produced a significant but smaller BOLD increase in the intact striatum and a symmetric bilateral increase in the motor cortex. The D2 family agonist quinpirole, which induced mild dyskinesia on chronic treatment, did not produce BOLD changes in the striatum or motor cortex. Further evidence to support an association between BOLD changes and dyskinesia comes from a direct correlation between scores of FD and magnitude of drug-induced BOLD increases in the denervated striatum and motor cortex. Our results suggest that striatal and cortical activation induced by stimulation of D1/D5 receptors has a primary role in the induction of peak dose dyskinesia in parkinsonism.

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Section: Severity Of Fd Is Related To Striatal and Motor Cortex Bold supporting

confidence: 68%

Mapping the Effects of Three Dopamine Agonists with Different Dyskinetogenic Potential and Receptor Selectivity Using Pharmacological Functional Magnetic Resonance Imaging

Delfino

Kalisch

Czisch

et al. 2007

Neuropsychopharmacol

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“…Timeline of experiments is depicted on Figure 1 B. Unilateral, 6-OHDA-lesioned, L-dopa/benserazidetreated rats were generated as described previously (Meissner et al, 2006). Male Wistar rats (Charles River, Kingston, NY) (250 -350 gm) were pretreated with desipramine (25 mg/kg, i.p.)…”

Section: Rat Studiesmentioning

confidence: 99%

RGS9–2 Negatively Modulates l-3,4-Dihydroxyphenylalanine-Induced Dyskinesia in Experimental Parkinson's Disease

Gold¹,

Hoang²,

Potts³

et al. 2007

J. Neurosci.

115

104

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Chronic L-dopa treatment of Parkinson's disease (PD) often leads to debilitating involuntary movements, termed L-dopa-induced dyskinesia (LID), mediated by dopamine (DA) receptors. RGS9 -2 is a GTPase accelerating protein that inhibits DA D2 receptor-activated G proteins. Herein, we assess the functional role of RGS9 -2 on LID. In monkeys, Western blot analysis of striatal extracts shows that RGS9 -2 levels are not altered by MPTP-induced DA denervation and/or chronic L-dopa administration. In MPTP monkeys with LID, striatal RGS9 -2 overexpression -achieved by viral vector injection into the striatum -diminishes the involuntary movement intensity without lessening the anti-parkinsonian effects of the D1/D2 receptor agonist L-dopa. In contrasts, in these animals, striatal RGS9 -2 overexpression diminishes both the involuntary movement intensity and the anti-parkinsonian effects of the D2/D3 receptor agonist ropinirole. In unilaterally 6-OHDA-lesioned rats with LID, we show that the time course of viral vector-mediated striatal RGS9 -2 overexpression parallels the time course of improvement of L-dopa-induced involuntary movements. We also find that unilateral 6-OHDA-lesioned RGS9 Ϫ/Ϫ mice are more susceptible to L-dopa-induced involuntary movements than unilateral 6-OHDA-lesioned RGS9 ϩ/ϩ mice, albeit the rotational behavior -taken as an index of the anti-parkinsonian response -is similar between the two groups of mice. Together, these findings suggest that RGS9 -2 plays a pivotal role in LID pathophysiology. However, the findings also suggest that increasing RGS9 -2 expression and/or function in PD patients may only be a suitable therapeutic strategy to control involuntary movements induced by nonselective DA agonist such as L-dopa.

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“…In vivo: 30 adult male Sprague Dawley rats (Charles River Laboratories) weighing 175-200 g at the beginning of the experiment were used. On day 0 of the protocol, unilateral dopamine deprivation of the striatum was obtained by 6-OHDA (3 g/l) injection in the right medial forebrain bundle (2.5 l at AP ϭ Ϫ3.7 mm, ML ϭ ϩ1.7 mm, and DV ϭ Ϫ8 mm, relative to bregma) as previously described (Meissner et al, 2006;Schuster et al, 2008;Berthet et al, 2009). Animals displaying a loss of TH-immunopositive fibers in the striatum Ͼ95% (Bezard et al, 2001b;Guigoni et al, 2005b), as assessed after completion of all experiments, were retained for final analysis.…”

Section: Rodent Experimentsmentioning

confidence: 99%

“…In such conditions, L-DOPA induces a gradual development of AIMs. On day 29, 10 rats were scored as dyskinetic (score ϭ 12) after observation by a trained investigator as previously described (Meissner et al, 2006;Schuster et al, 2008;Schuster et al, 2009), using a validated rating scale (Cenci et al, 1998;Lundblad et al, 2002). On day 30, all animals received the last vehicle injection ϩ/Ϫ L-DOPA.…”

Section: Rodent Experimentsmentioning

confidence: 99%

“…Interestingly, L-DOPA-induced dyskinesia (LID) in PD, associated with chronic stimulation of dopamine receptors, correlates with an increased membranous localization of D1R (Guigoni et al, 2007;Berthet et al, 2009). Since dopamine, the natural agonist of the receptor, is present in large amounts after L-DOPA administration (Meissner et al, 2006), the D1R should internalize as would any G-protein-coupled receptor in the condition of overstimulation. Such impairment in receptor fate therefore suggests the contribution of an altered proteasome function, a key feature that has yet to be explored.…”

Section: Introductionmentioning

confidence: 99%

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l-DOPA Impairs Proteasome Activity in Parkinsonism through D₁Dopamine Receptor

Berthet¹,

Bézard²,

Porras³

et al. 2012

J. Neurosci.

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Aberrant membrane localization of dopamine D 1 receptor (D1R) is associated with L-DOPA-induced dyskinesia (LID), a major complication of L-DOPA treatment in Parkinson's disease (PD). Since the proteasome plays a central role in modulating neuronal response through regulation of neurotransmitter receptor intraneuronal fate, we hypothesized that the ubiquitine-proteasome proteolytic pathway could be impaired in LID. Those LIDs are actually associated with a striatum-specific decrease in proteasome catalytic activity and accumulation of polyubiquitinated proteins in experimental rodent and monkey parkinsonism. We then demonstrated that such decreased proteasome catalytic activity (1) results from D1R activation and (2) feed-back the D1R abnormal trafficking, i.e., its exaggerated cell surface abundance. We further showed that the genetic invalidation of the E3 ubiquitin-protein ligase parkin PD gene leads to exaggerated abnormal involuntary movements compared with wild-type mice. We thus established in an unprecedented series of experimental models that impairment of the ubiquitine-proteasome system at specific nodes (E3 ligase parkin, polyubiquitination, proteasome catalytic activity) leads to the same phenomenon, i.e., aberrant behavioral response to dopamine replacement therapy in PD, highlighting the intimate interplay between dopamine receptor and proteasome activity in a nondegenerative context.

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Increased slow oscillatory activity in substantia nigra pars reticulata triggers abnormal involuntary movements in the 6-OHDA-lesioned rat in the presence of excessive extracelullar striatal dopamine

Cited by 139 publications

References 49 publications

Mapping the Effects of Three Dopamine Agonists with Different Dyskinetogenic Potential and Receptor Selectivity Using Pharmacological Functional Magnetic Resonance Imaging

Mapping the Effects of Three Dopamine Agonists with Different Dyskinetogenic Potential and Receptor Selectivity Using Pharmacological Functional Magnetic Resonance Imaging

RGS9–2 Negatively Modulates l-3,4-Dihydroxyphenylalanine-Induced Dyskinesia in Experimental Parkinson's Disease

l-DOPA Impairs Proteasome Activity in Parkinsonism through D₁Dopamine Receptor

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Increased slow oscillatory activity in substantia nigra pars reticulata triggers abnormal involuntary movements in the 6-OHDA-lesioned rat in the presence of excessive extracelullar striatal dopamine

Cited by 139 publications

References 49 publications

Mapping the Effects of Three Dopamine Agonists with Different Dyskinetogenic Potential and Receptor Selectivity Using Pharmacological Functional Magnetic Resonance Imaging

Mapping the Effects of Three Dopamine Agonists with Different Dyskinetogenic Potential and Receptor Selectivity Using Pharmacological Functional Magnetic Resonance Imaging

RGS9–2 Negatively Modulates l-3,4-Dihydroxyphenylalanine-Induced Dyskinesia in Experimental Parkinson's Disease

l-DOPA Impairs Proteasome Activity in Parkinsonism through D1Dopamine Receptor

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l-DOPA Impairs Proteasome Activity in Parkinsonism through D₁Dopamine Receptor