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Neurophysiological treatment effects of mesdopetam, pimavanserin and clozapine in a rodent model of Parkinson's disease psychosis.
Stan, Tiberiu Loredan; Ronaghi, Abdolaziz; Barrientos, Sebastian A; Halje, Pär; Censoni, Luciano; Garro-Martínez, Emilio; Nasretdinov, Azat; Malinina, Evgenya; Hjorth, Stephan; Svensson, Peder; Waters, Susanna; Sahlholm, Kristoffer; Petersson, Per.
Afiliación
  • Stan TL; The Group for Integrative Neurophysiology and Neurotechnology, Department of Experimental Medical Science, Lund University, Lund, Sweden.
  • Ronaghi A; The Group for Integrative Neurophysiology, Department of Medical and Translational Biology, Umeå University, Umeå, Sweden.
  • Barrientos SA; The Group for Integrative Neurophysiology and Neurotechnology, Department of Experimental Medical Science, Lund University, Lund, Sweden.
  • Halje P; The Group for Integrative Neurophysiology and Neurotechnology, Department of Experimental Medical Science, Lund University, Lund, Sweden.
  • Censoni L; The Group for Integrative Neurophysiology, Department of Medical and Translational Biology, Umeå University, Umeå, Sweden.
  • Garro-Martínez E; The Group for Integrative Neurophysiology, Department of Medical and Translational Biology, Umeå University, Umeå, Sweden; Department of Medical and Translational Biology, Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden.
  • Nasretdinov A; The Group for Integrative Neurophysiology, Department of Medical and Translational Biology, Umeå University, Umeå, Sweden.
  • Malinina E; The Group for Integrative Neurophysiology, Department of Medical and Translational Biology, Umeå University, Umeå, Sweden.
  • Hjorth S; Integrative Research Laboratories Sweden AB, Göteborg, Sweden.
  • Svensson P; Integrative Research Laboratories Sweden AB, Göteborg, Sweden.
  • Waters S; Integrative Research Laboratories Sweden AB, Göteborg, Sweden.
  • Sahlholm K; Department of Medical and Translational Biology, Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden; Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden.
  • Petersson P; The Group for Integrative Neurophysiology, Department of Medical and Translational Biology, Umeå University, Umeå, Sweden; The Group for Integrative Neurophysiology and Neurotechnology, Department of Experimental Medical Science, Lund University, Lund, Sweden. Electronic address: Per.Petersson@umu.s
Neurotherapeutics ; 21(2): e00334, 2024 Mar.
Article en En | MEDLINE | ID: mdl-38368170
ABSTRACT
Psychosis in Parkinson's disease is a common phenomenon associated with poor outcomes. To clarify the pathophysiology of this condition and the mechanisms of antipsychotic treatments, we have here characterized the neurophysiological brain states induced by clozapine, pimavanserin, and the novel prospective antipsychotic mesdopetam in a rodent model of Parkinson's disease psychosis, based on chronic dopaminergic denervation by 6-OHDA lesions, levodopa priming, and the acute administration of an NMDA antagonist. Parallel recordings of local field potentials from eleven cortical and sub-cortical regions revealed shared neurophysiological treatment effects for the three compounds, despite their different pharmacological profiles, involving reversal of features associated with the psychotomimetic state, such as a reduction of aberrant high-frequency oscillations in prefrontal structures together with a decrease of abnormal synchronization between different brain regions. Other drug-induced neurophysiological features were more specific to each treatment, affecting network oscillation frequencies and entropy, pointing to discrete differences in mechanisms of action. These findings indicate that neurophysiological characterization of brain states is particularly informative when evaluating therapeutic mechanisms in conditions involving symptoms that are difficult to assess in rodents such as psychosis, and that mesdopetam should be further explored as a potential novel antipsychotic treatment option for Parkinson psychosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Éteres Fenílicos / Piperidinas / Propilaminas / Trastornos Psicóticos / Antipsicóticos / Urea / Clozapina Límite: Animals Idioma: En Revista: Neurotherapeutics Asunto de la revista: NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Éteres Fenílicos / Piperidinas / Propilaminas / Trastornos Psicóticos / Antipsicóticos / Urea / Clozapina Límite: Animals Idioma: En Revista: Neurotherapeutics Asunto de la revista: NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos