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Static, Low-Frequency, and Pulsed Magnetic Fields in Biological Systems
Published in James C. Lin, Electromagnetic Fields in Biological Systems, 2016
Strafella, Ko, and Monchi (2006) examined placebo effects on patients with PD using sham rTMS (placebo-rTMS) alone. The authors measured the changes in striatal [11C] raclopride binding potentials (BP) together with positron emission tomography (PET). Placebo-rTMS induced significant bilateral reduction in [11C] raclopride BP in dorsal and ventral striatum as compared with the baseline condition. This reduction in BP is indicative of an increase in dopamine neurotransmission. The changes in [11C] raclopride binding were more evident in the hemisphere contralateral to the more affected side, supporting the hypothesis that the more severe the symptoms the greater the drive for symptom relief and therefore the placebo response. This is the first study addressing the placebo contribution during rTMS. Although the results seemed to confirm earlier evidence that expectation induces dopaminergic placebo effects, they also suggested the importance of placebo-controlled studies in future clinical trials involving brain stimulation techniques.
Applications for Drug Development
Published in George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos, Handbook of Small Animal Imaging, 2018
Jessica Kalra, Donald T. Yapp, Murray Webb, Marcel B. Bally
The etiology of Parkinson’s disease remains under investigation. Both genetic (Parkin, Alpha synuclein) and environmental factors (pesticides, head trauma) have been implicated in this disease. The major clinical features of Parkinson’s disease include tremor, muscle rigidity, bradykinesia, postural instability, and cognitive deficits. Postmortem examinations of cortical tissues show degeneration of dopamine neurons in the substantia nigra. Experimental rodent models of Parkinson’s disease can be successfully induced using chemicals (6-hydroxydopamine [6-OHDA], 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, rotenone, paraquat, or epoxomicin) or genetically (α-synuclein knock-in mice or DJ-1 knock-out mice) (Garcia-Alloza and Bacskai 2004). For each model, only some neuropathological and behavioral phenotypes may be present, and no single model is able to recapitulate all of the features of Parkinson’s disease. Nevertheless, MRI has been successfully used to study anatomical or morphological changes in vivo, while PET and SPECT have provided valuable insights into the mechanisms of nigrostriatal degeneration in animal models of Parkinson’s disease. For example, in 2007, Pellegrino et al. used PET to investigate dopamine transporter status using (11)C-2β-carbomethoxy-3β-(4-fluorophenyl)-tropane as well as dopamine receptor modulation using (11)C-raclopride in a 6-OHDA model of Parkinson’s disease (Pellegrino et al. 2007). A group led by Prof. Muller from the Clinic of Nuclear Medicine, University Hospital, Düsseldorf, Germany, has been working on nuclear imaging techniques to examine a variety of neurodegenerative diseases including Parkinson’s disease. In several publications, Muller’s group describes the molecular imaging of the dopaminergic synapse in vivo. In one paper published in 2011 (Nikolaus et al. 2011), this group used a series of radionuclides to examine DA transporter (DAT) and/or Dopamine (2) receptor binding with SPECT or PET in a 6-OHDA rat model. Interestingly, their studies were conducted before and after treatment with haloperidol, l-DOPA, and methylphenidate, the gold standard therapies for Parkinson’s disease.
Cognitive flexibility in humans and other laboratory animals
Published in Journal of the Royal Society of New Zealand, 2021
Quenten Highgate, Susan Schenk
A role of dopamine in different subregions of the striatum has also been suggested. Dorsomedial administration of a dopamine neurotoxin (O’Neill and Brown 2007; Tait et al. 2017; Grospe et al. 2018) and local infusions of the dopamine D2 receptor antagonist, raclopride, impaired reversal learning in rodents (Sala-bayo et al. 2020). This is consistent with the suggested role of dopamine in the dorsomedial striatum of non-human primates. In this species, neurotoxic dopamine lesions also impaired reversal learning (Clarke et al. 2011), abnormally low or high dopamine levels were associated with impaired reversal learning (Groman et al. 2013), and dopamine D2 receptor density was positively associated with reversal learning performance (Groman et al. 2011). In the NAC, locally infused dopamine D2 agonists impaired set shifting and reversal learning in rodents (Haluk and Floresco 2009), but locally infused D2 antagonists produced equivocal results (Haluk and Floresco 2009; Sala-bayo et al. 2020).