Imaging DA release in a rat model of L-DOPA-induced dyskinesias: A longitudinal in vivo PET investigation of the antidyskinetic effect of MDMA

Lettfuss, Nadine Y.; Fischer, Karl-Georg; Pichler, Bernd J.; Ameln-Mayerhofer, Andreas von

doi:10.1016/j.neuroimage.2012.06.051

Cited by 13 publications

(10 citation statements)

References 76 publications

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“…Studies using PET in 6-OHDA lesioned rats chronically treated with l -DOPA and displaying severe AIMs (the rodent LID phenotype) display regional increases in CBF (measured using [14C]-iodoantipyrine uptake), increases in regional cerebral glucose utilization (rCGU; measured using [14C]-2-deoxyglucose uptake) and DA release (measured using displacement of [11C]-raclopride binding potential), consistent with similar findings in PD patients (143–145). To date however, no studies have assessed the impact of l -DOPA treatment on brain morphometry or relaxation time in either rodent or primates, using advanced structural MR imaging methods.…”

Section: Future Directions: a Translational Road Map To Bridge Animalsupporting

confidence: 68%

“…Indeed, as previously stated, the use of clinically comparable technology (MRI) to conduct parallel assessments in experimental animals and humans is likely to accelerate translation of basic findings to the clinic. Neuroimaging tools may therefore play a critical role in future studies evaluating not only target engagement, but also drug efficacy in models of LID, as evidenced by recent studies using PET (143, 144, 146). No studies as yet have employed MRI methods, but the potential for application of this technology is apparent.…”

Section: Future Directions: a Translational Road Map To Bridge Animalmentioning

confidence: 99%

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Brain Morphometry and the Neurobiology of Levodopa-Induced Dyskinesias: Current Knowledge and Future Potential for Translational Pre-Clinical Neuroimaging Studies

2014

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Dopamine replacement therapy in the form of levodopa results in a significant proportion of patients with Parkinson’s disease developing debilitating dyskinesia. This significantly complicates further treatment and negatively impacts patient quality of life. A greater understanding of the neurobiological mechanisms underlying levodopa-induced dyskinesia (LID) is therefore crucial to develop new treatments to prevent or mitigate LID. Such investigations in humans are largely confined to assessment of neurochemical and cerebrovascular blood flow changes using positron emission tomography and functional magnetic resonance imaging. However, recent evidence suggests that LID is associated with specific morphological changes in the frontal cortex and midbrain, detectable by structural MRI and voxel-based morphometry. Current human neuroimaging methods however lack sufficient resolution to reveal the biological mechanism driving these morphological changes at the cellular level. In contrast, there is a wealth of literature from well-established rodent models of LID documenting detailed post-mortem cellular and molecular measurements. The combination therefore of advanced neuroimaging methods and rodent LID models offers an exciting opportunity to bridge these currently disparate areas of research. To highlight this opportunity, in this mini-review, we provide an overview of the current clinical evidence for morphological changes in the brain associated with LID and identify potential cellular mechanisms as suggested from human and animal studies. We then suggest a framework for combining small animal MRI imaging with rodent models of LID, which may provide important mechanistic insights into the neurobiology of LID.

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Section: Future Directions: a Translational Road Map To Bridge Animalsupporting

confidence: 68%

Section: Future Directions: a Translational Road Map To Bridge Animalmentioning

confidence: 99%

Brain Morphometry and the Neurobiology of Levodopa-Induced Dyskinesias: Current Knowledge and Future Potential for Translational Pre-Clinical Neuroimaging Studies

2014

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“…For comparison, BP ND s derived from the late phase (starting at 20 min p.i. ), with fixed tissue‐to‐plasma clearance (k 2 ′ = 0.24/min) and referenced to the cerebellum, were determined via Logan reference modeling (Lettfuss, Fischer, Sossi, Pichler, & von Ameln‐Mayerhofer, ).…”

Section: Methodsmentioning

confidence: 99%

Intrastriatal administration of botulinum neurotoxin A normalizes striatal D₂R binding and reduces striatal D₁R binding in male hemiparkinsonian rats

Wedekind

Oskamp

Lang

et al. 2017

J of Neuroscience Research

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Cerebral administration of botulinum neurotoxin A (BoNT-A) has been shown to improve disease-specific motor behavior in a rat model of Parkinson disease (PD). Since the dopaminergic system of the basal ganglia fundamentally contributes to motor function, we investigated the impact of BoNT-A on striatal dopamine receptor expression using in vitro and in vivo imaging techniques (positron emission tomography and quantitative autoradiography, respectively). Seventeen male Wistar rats were unilaterally lesioned with 6-hydroxydopamine (6-OHDA) and assigned to two treatment groups 7 weeks later: 10 rats were treated ipsilaterally with an intrastriatal injection of 1 ng BoNT-A, while the others received vehicle (n 5 7). All animals were tested for asymmetric motor behavior (apomorphine-induced rotations and forelimb usage) and

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“…significantly alleviated L-DOPA-induced AIMs severity but had no effect on L-DOPA-induced rotations [175]. In another study, racemic MDMA (10 mg/kg s.c.) significantly alleviated L-DOPA-induced AIMs and established that the antidyskinetic efficacy of racemic MDMA was not related to striatal dopamine levels, as dopamine levels in the striatum were higher in animals treated with MDMA and L-DOPA than in animals treated with L-DOPA alone [741]. Heterozygous and homozygous parkin knockout mice are more likely to develop MDMA-induced hyperthermia (30 mg/kg i.p.)…”

Section: Dat = Net = Sert Inhibitorsmentioning

confidence: 99%

Monoamine Reuptake Inhibitors in Parkinson’s Disease

Huot

Fox

Brotchie

2015

Parkinson's Disease

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The motor manifestations of Parkinson's disease (PD) are secondary to a dopamine deficiency in the striatum. However, the degenerative process in PD is not limited to the dopaminergic system and also affects serotonergic and noradrenergic neurons. Because they can increase monoamine levels throughout the brain, monoamine reuptake inhibitors (MAUIs) represent potential therapeutic agents in PD. However, they are seldom used in clinical practice other than as antidepressants and wake-promoting agents. This review article summarises all of the available literature on use of 50 MAUIs in PD. The compounds are divided according to their relative potency for each of the monoamine transporters. Despite wide discrepancy in the methodology of the studies reviewed, the following conclusions can be drawn: (1) selective serotonin transporter (SERT), selective noradrenaline transporter (NET), and dual SERT/NET inhibitors are effective against PD depression; (2) selective dopamine transporter (DAT) and dual DAT/NET inhibitors exert an anti-Parkinsonian effect when administered as monotherapy but do not enhance the anti-Parkinsonian actions of L-3,4-dihydroxyphenylalanine (L-DOPA); (3) dual DAT/SERT inhibitors might enhance the anti-Parkinsonian actions of L-DOPA without worsening dyskinesia; (4) triple DAT/NET/SERT inhibitors might exert an anti-Parkinsonian action as monotherapy and might enhance the anti-Parkinsonian effects of L-DOPA, though at the expense of worsening dyskinesia.

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Imaging DA release in a rat model of L-DOPA-induced dyskinesias: A longitudinal in vivo PET investigation of the antidyskinetic effect of MDMA

Cited by 13 publications

References 76 publications

Brain Morphometry and the Neurobiology of Levodopa-Induced Dyskinesias: Current Knowledge and Future Potential for Translational Pre-Clinical Neuroimaging Studies

Brain Morphometry and the Neurobiology of Levodopa-Induced Dyskinesias: Current Knowledge and Future Potential for Translational Pre-Clinical Neuroimaging Studies

Intrastriatal administration of botulinum neurotoxin A normalizes striatal D₂R binding and reduces striatal D₁R binding in male hemiparkinsonian rats

Monoamine Reuptake Inhibitors in Parkinson’s Disease

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Imaging DA release in a rat model of L-DOPA-induced dyskinesias: A longitudinal in vivo PET investigation of the antidyskinetic effect of MDMA

Cited by 13 publications

References 76 publications

Brain Morphometry and the Neurobiology of Levodopa-Induced Dyskinesias: Current Knowledge and Future Potential for Translational Pre-Clinical Neuroimaging Studies

Brain Morphometry and the Neurobiology of Levodopa-Induced Dyskinesias: Current Knowledge and Future Potential for Translational Pre-Clinical Neuroimaging Studies

Intrastriatal administration of botulinum neurotoxin A normalizes striatal D2R binding and reduces striatal D1R binding in male hemiparkinsonian rats

Monoamine Reuptake Inhibitors in Parkinson’s Disease

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Intrastriatal administration of botulinum neurotoxin A normalizes striatal D₂R binding and reduces striatal D₁R binding in male hemiparkinsonian rats