Antagonising the serotonin 2A (5-HT) receptor is an efficacious way to alleviate dyskinesia and psychosis in Parkinson's disease (PD). However, previous research indicates that there might be a limit to the effects conferred by this approach. 5-HT receptors were shown to form hetero-dimers with metabotropic glutamate 2 (mGlu) receptors, in which 5-HT blockade and mGlu activation elicit equivalent effects at the downstream signalling level. We have previously shown that mGlu activation reduces both dyskinesia and psychosis-like behaviours (PLBs) induced by L-3,4-dihydroxyphenylalanine (l-DOPA), in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate. Here, we hypothesised that concurrent 5-HT antagonism and mGlu activation would provide greater anti-dyskinetic and anti-psychotic benefits than either approach alone. We conducted 3 series of experiments in the MPTP-lesioned marmoset. In the first series of experiments, the mGlu positive allosteric modulator LY-487,379 and the 5-HT antagonist EMD-281,014, either alone or in combination, were added to l-DOPA. In the second series of experiments, the mGlu orthosteric agonist LY-354,740 and EMD-281,014, either alone or in combination, were added to l-DOPA. In the last series of experiments, we investigated whether mGlu blockade would diminish the effects of antagonising 5-HT receptors. To this end, the mGlu orthosteric antagonist LY-341,495 and EMD-281,014, either alone or in combination, were added to l-DOPA. We found that the anti-dyskinetic effect of the combination LY-487,379/EMD-281,014 was greater than the ones conferred by LY-487,379 (by 35%, P < 0.05) and EMD-281,014 (by 38%, P < 0.01). The anti-dyskinetic and anti-psychotic effects of the combination LY-354,740/EMD-281,014 were also greater than the ones conferred by LY-354,740 (by 57% for dyskinesia and 54% for PLBs, both P < 0.001) and EMD-281,014 (by 61% for dyskinesia and 53% for PLBs, both P < 0.001). The anti-parkinsonian action of l-DOPA was maintained with all treatments. Lastly, the addition of LY-341,495 abolished the therapeutic effects of EMD-281,014 on dyskinesia and PLBs. Our results suggest that mGlu activation may enhance the anti-dyskinetic and anti-psychotic effects of 5-HT blockade and could provide relief to PD patients with dyskinesia and psychotic symptoms beyond what can be achieved with current therapies.
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http://dx.doi.org/10.1016/j.neuropharm.2021.108465 | DOI Listing |
Food Funct
December 2024
Department of Oral and Maxillofacial & Head and Neck Oncology, Beijing Stomatological Hospital, Capital Medical University, Tian Tan Xi Li No. 4, Beijing, 100050, China.
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by synovial inflammation, cartilage damage, and bone loss. Although effective treatments are currently lacking, early interventions hold promise for alleviating RA symptoms. Inorganic nitrates and vitamin C (VC) are essential bioactive substances abundant in fruits and vegetables.
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December 2024
Universidade de Lisboa, Centro de Linguística, Lisbon, Portugal.
Most natural languages have more than one linguistic form available to express disjunction. One of these forms is often reported by native speakers to be more exclusive than the other(s) and, in recent years, it has been claimed that some languages may in fact have dedicated exclusive disjunctions. In this paper, we report on a series of experiments testing this claim across five languages of primary interest.
View Article and Find Full Text PDFOpen Mind (Camb)
December 2024
University of Bern, Bern, Switzerland.
Task adaptation, characterized by a progressive increase in speed throughout experimental trials, has been extensively observed across various paradigms. Yet, the underlying mechanisms driving this phenomenon remain unclear. According to the learning-based explanation, participants are implicitly learning, becoming more proficient over time.
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December 2024
Department of Medicine, Rowan-Virtua School of Osteopathic Medicine, Stratford, NJ, USA.
Aims: Post-mastectomy pain syndrome is a common postoperative complication that can impact patient quality of life and function. The aim of this systematic review is to evaluate the effectiveness of cryoneurolysis as an intervention for the management of post-mastectomy pain.
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Sci Data
December 2024
Paris-Lodron-University of Salzburg, Department of Psychology, Centre for Cognitive Neuroscience, Salzburg, Austria.
Experimental design in language cognition research often involves presenting language material while measuring associated behavior and/or neural activity. To make the collected data easily and fully analyzable by both the original data authors and others, it is important to have detailed information about the stimulus presentation events, including the nature and properties of the presented stimuli, using a common vocabulary and syntax. We present HED LANG, a library extension of the Hierarchical Event Descriptors (HED) event annotation schema for time series behavioral and neuroimaging data.
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