Altered behavioral responses mediated by serotonin receptors in the genetically dystonic (dt) rat

Wieland, Scott; Lucki, Irwin

doi:10.1016/0361-9230(91)90185-m

Cited by 14 publications

(3 citation statements)

References 33 publications

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“…Rats depleted of serotoninergic neurons show no abnormality of baseline movement (14). Yet the genetically dystonic rat has diminished motor responses that involve serotoninergic systems and increased sensitivity to 5-HT 1A serotoninergic agonists (15), and the genetically dystonic hamster is dramatically worsened by 5-HT 1A antagonists (16). In humans, the serotonin syndrome is becoming increasingly recognized in patients taking drugs that increase synaptic serotonin or stimulate serotonin receptors (17,18).…”

mentioning

confidence: 99%

Selective Decrease in Central Nervous System Serotonin Turnover in Children with Dopa-Nonresponsive Dystonia

Assmann

Köhler

Hoffmann³

et al. 2002

Pediatr Res

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Childhood dystonia that does not respond to treatment with levodopa (dopa-nonresponsive dystonia, DND) has an unclear pathogenesis and is notoriously difficult to treat. To test the hypothesis that there may be abnormalities in serotonin turnover in DND we measured cerebrospinal fluid (CSF) concentrations of homovanillic (HVA) and 5-hydroxyindoleacetic (HIAA) acids, metabolites of dopamine and serotonin, respectively, in 18 children with dystonia not responsive to levodopa. These were combined with a reference population of 85 children with neurologic or metabolic disease known not to affect dopamine or serotonin metabolism. Because of the known natural age-related decrement in HVA and HIAA concentrations, the results were analyzed using multiple regression using age and DND as predictors of CSF HIAA and HVA concentrations. DND was a highly significant predictor of CSF HIAA concentration (p Ͻ 0.001) but not of CSF HVA concentration (p ϭ 0.59). After fitting a regression model, the geometric mean ratio of CSF HIAA in DND compared with the reference range was 0.53 whereas that for CSF HVA was 0.95. We also analyzed CSF HIAA/HVA ratios. After fitting a regression model, we found no dependence on age, and the mean of CSF HIAA/HVA in DND was 0.28 whereas that for the reference range was 0.49 (p Ͻ 0.001). We conclude that a significant number of children with DND have reduced CNS serotonin turnover. Treatment with drugs that increase serotonin concentration in the synaptic cleft should be considered in this group of patients. Childhood dystonias can pragmatically be divided into those that respond to treatment with levodopa and those that do not. Those that do respond to levodopa usually have some parkinsonian features and have been termed parkinsonism-dystonia. Parkinsonism-dystonia syndromes are often caused by deficiency of the neurotransmitter dopamine resulting from inborn errors of the dopamine biosynthesis pathways (1, 2). Dystonia that does not respond to levodopa has a wide variety of causes, and its pathogenesis is poorly understood. Although the study of the acidic metabolites of dopamine and the individual pterin species in human CSF has been fruitful in understanding the mechanisms causing parkinsonism-dystonia in children and young adults (1,(3)(4)(5), it has been disappointing in other movement disorders such as DND. This latter group of patients is also notoriously difficult to treat.Serotonin and dopamine metabolism in the brain are closely linked at both a biochemical and at a physiologic level (6, 7). The basal ganglia of both animals and man have a large serotoninergic projection from the midbrain raphe nuclei (8 -12). However, the function of this in the control of movement is not entirely clear. Impaired CNS serotonin metabolism has been found in adult-onset idiopathic focal dystonias (13). Rats depleted of serotoninergic neurons show no abnormality of baseline movement (14). Yet the genetically dystonic rat has diminished motor responses that involve serotoninergic systems and increased sensitiv...

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confidence: 99%

Selective Decrease in Central Nervous System Serotonin Turnover in Children with Dopa-Nonresponsive Dystonia

Assmann

Köhler

Hoffmann³

et al. 2002

Pediatr Res

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“…Serotonin spielt eine Rolle in der autonomen Kontrolle der Atmung, Temperatur und Stimmung (8). Es scheint jedoch eine zusätzliche Bedeutung in der motorischen Kontrolle sehr wahrscheinlich (40). Sowohl Dopamin als auch Serotonin besitzen bereits in der frühembryonalen Entwicklung eine Bedeutung für die neuronale Entwicklung und Verschaltung (13).…”

Section: Amine Und Pterineunclassified

Leukodystrophien und Neurotransmitterstörungen

Assmann¹,

Bültmann²,

Krägeloh‐Mann³

et al. 2018

Nervenheilkunde

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ZusammenfassungIn diesem Artikel werden beispielhaft zwei Gruppen von angeborenen Erkrankungen dargestellt, die sich vom Säuglingsalter bis zum Erwachsenenalter hin manifestieren können. Die Leukodystrophien sind neurodegenerative Erkrankungen, für die zum Teil experimentelle Therapieansätze entwickelt werden. Für die Gruppe der angeborenen Störungen im Stoffwechsel der biogenen Amine steht bei einigen Defekten mit L-Dopa eine effiziente Therapie zur Verfügung, deren Einsatz so früh wie möglich und lebenslang erfolgen sollte, um irreversible Entwicklungsstörungen und Bewegungsstörungen zu vermeiden.

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“…7 In addition, a study showed that genetically dystonic rats had a sixfold increase in the tendency to develop dystonia-like behavior when exposed to a 5-HT 1A agonist, compared with their normal littermates. 8 Given its high affinity and partial agonism at D 2 and 5-HT 1A receptors, 2 brexpiprazole, possibly influenced by predispositions such as metabolism and genetics, could destabilize direct and indirect pathways, resulting in dystonia. Meanwhile, our case indicates that some patients beginning clozapine for tardive dystonia might need lower serum levels than the therapeutic reference range (350-600 ng/mL), which, for Japanese patients, has been supported solely by one cross-sectional study that did not include those intolerant to adequate antipsychotic doses due to EPS.…”

mentioning

confidence: 99%

Brexpiprazole‐related tardive dystonia in a young patient with schizophrenia: A case report

Ebina,

Iwamoto,

Ikeda

2024

Psychiatry Clin Neurosci

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Altered behavioral responses mediated by serotonin receptors in the genetically dystonic (dt) rat

Cited by 14 publications

References 33 publications

Selective Decrease in Central Nervous System Serotonin Turnover in Children with Dopa-Nonresponsive Dystonia

Selective Decrease in Central Nervous System Serotonin Turnover in Children with Dopa-Nonresponsive Dystonia

Leukodystrophien und Neurotransmitterstörungen

Brexpiprazole‐related tardive dystonia in a young patient with schizophrenia: A case report

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