Neurophysiological treatment effects of mesdopetam, pimavanserin and clozapine in a rodent model of Parkinson's disease psychosis

Tiberiu Loredan Stan, Abdolaziz Ronaghi, Sebastian A Barrientos, Pär Halje, Luciano Censoni, Emilio Garro-Martínez, Azat Nasretdinov, Evgenya Malinina, Stephan Hjorth, Peder Svensson, Susanna Waters, Kristoffer Sahlholm, Per Petersson

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article numbere00334
Pages (from-to)1-12
Issue number2
Publication statusPublished - 2024 Mar

Subject classification (UKÄ)

  • Pharmaceutical Sciences
  • Neurosciences

Free keywords

  • Animals
  • Clozapine/pharmacology
  • Parkinson Disease/complications
  • Antipsychotic Agents/pharmacology
  • Rodentia
  • Prospective Studies
  • Psychotic Disorders/etiology
  • Phenyl Ethers
  • Piperidines
  • Propylamines
  • Urea/analogs & derivatives


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