The serotonergic system in motor and non-motor manifestations of Parkinson's disease
Identifieur interne : 001036 ( Main/Exploration ); précédent : 001035; suivant : 001037The serotonergic system in motor and non-motor manifestations of Parkinson's disease
Auteurs : Philippe Huot [Canada] ; Susan H. Fox [Canada]Source :
- Experimental brain research [ 0014-4819 ] ; 2013.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
The understanding of Parkinson's disease (PD) classically revolves around dopamine depletion within the striatum. However, PD is a multi-systemic disease in which extra-dopaminergic systems are affected. The serotonergic (5-HT) system is one of these and has been extensively studied in PD. Although the 5-HT system uses one transporter (SERT) and 14 receptor sub-types, most of the studies in PD have focussed on SERT and serotonergic type 1A and 2A receptors (5-HT1A and 5-HT2A). Post-mortem autoradiographic binding studies and in vivo imaging studies have suggested an involvement of the 5-HT system in PD-related anxiety, depression, psychosis and L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia. Pre-clinical and clinical pharmacological studies have shown that SERT blockade might effectively alleviate depression and dyskinesia and, more recently, might exert disease-modifying effects. Enhancing the physiological activity of 5-HT1A receptors with 5-HT1A agonists might alleviate anxiety, dyskinesia and tremor, although a deleterious effect on the anti-parkinsonian efficacy of L-DOPA may ultimately limit the use of this class of compounds. Enhanced 5-HT2A-mediated neurotransmission has been associated with depression, dyskinesia, psychosis and tremor. The current article critically reviews studies assessing the SERT, as well as 5-HT1A and 5-HT2A receptors in idiopathic PD and animal models of PD, and discusses unmet challenges to effectively treat manifestations of PD using SERT antagonists, 5-HT1A agonists and 5-HT2A antagonists.
Affiliations:
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However, PD is a multi-systemic disease in which extra-dopaminergic systems are affected. The serotonergic (5-HT) system is one of these and has been extensively studied in PD. Although the 5-HT system uses one transporter (SERT) and 14 receptor sub-types, most of the studies in PD have focussed on SERT and serotonergic type 1A and 2A receptors (5-HT<sub>1A</sub> and 5-HT<sub>2A</sub>). Post-mortem autoradiographic binding studies and in vivo imaging studies have suggested an involvement of the 5-HT system in PD-related anxiety, depression, psychosis and L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia. Pre-clinical and clinical pharmacological studies have shown that SERT blockade might effectively alleviate depression and dyskinesia and, more recently, might exert disease-modifying effects. Enhancing the physiological activity of 5-HT<sub>1A</sub> receptors with 5-HT<sub>1A</sub> agonists might alleviate anxiety, dyskinesia and tremor, although a deleterious effect on the anti-parkinsonian efficacy of L-DOPA may ultimately limit the use of this class of compounds. Enhanced 5-HT<sub>2A</sub>-mediated neurotransmission has been associated with depression, dyskinesia, psychosis and tremor. The current article critically reviews studies assessing the SERT, as well as 5-HT<sub>1A</sub> and 5-HT<sub>2A</sub> receptors in idiopathic PD and animal models of PD, and discusses unmet challenges to effectively treat manifestations of PD using SERT antagonists, 5-HT<sub>1A</sub> agonists and 5-HT<sub>2A</sub> antagonists.</div></front></TEI><affiliations><list><country><li>Canada</li></country><region><li>Ontario</li></region><settlement><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><country name="Canada"><noRegion><name sortKey="Huot, Philippe" sort="Huot, Philippe" uniqKey="Huot P" first="Philippe" last="Huot">Philippe Huot</name></noRegion><name sortKey="Fox, Susan H" sort="Fox, Susan H" uniqKey="Fox S" first="Susan H." last="Fox">Susan H. Fox</name><name sortKey="Huot, Philippe" sort="Huot, Philippe" uniqKey="Huot P" first="Philippe" last="Huot">Philippe Huot</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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