Orexin’s role in mouse behavioral endophenotypes for schizophrenia

• Applicant: Professor Dr. Markus Fendt
• Subject Area: Biological Psychiatry ; Cognitive, Systems and Behavioural Neurobiology
• Term: from 2019 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 424697493

• Final Report Year: 2023

Final Report Abstract

Taken together, the data from the first funding period indicate sex-dependent effects of orexin deficiency, nasal orexin, and specific OxR antagonists. Overall, male mice seem to more profit from orexin deficiency or OxR blockade while nasal orexin or chemogenetic stimulation of the orexin system had rather negative consequences. This was different in female mice, in which orexin deficiency or OxR blockade often had negative consequences. However, these statements are mainly based on our experiments regarding endophenotypes related to positive and negative symptoms of schizophrenia. Regarding endophenotypes of cognitive symptoms of schizophrenia clearly more data are needed to support these statements, especially from experiments investigating the role of OX1R and OX2R in these endophenotypes. Furthermore, the role of orexin in further cognitive functions – beyond ASST and 5-CSRTT – should be investigated. Last, we think it is crucial to test orexin-related treatments in a developmental animal model of schizophrenia.

Publications

• Orexin deficiency modulates cognitive flexibility in a sex‐dependent manner. Genes, Brain and Behavior, 20(3).
  Durairaja, Archana & Fendt, Markus
  
• Orexin deficiency affects sociability and the acquisition, expression, and extinction of conditioned social fear. Brain Research, 1751, 147199.
  Faesel, Nadine; Kolodziejczyk, Malgorzata H.; Koch, Michael & Fendt, Markus
  
• Intracerebroventricular infusion of the selective orexin 1 receptor antagonist SB-334867 impairs cognitive flexibility in a sex-dependent manner. Behavioural Brain Research, 424, 113791.
  Durairaja, Archana; Steinecke, Ceylan-Scarlett & Fendt, Markus
  
• Orexin deficiency affects sensorimotor gating and its amphetamine-induced impairment. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 116, 110517.
  Demidova, Alexandrina; Kahl, Evelyn & Fendt, Markus
  
• Sex-dependent role of orexin deficiency in feeding behavior and affective state of mice following intermittent access to a Western diet – Implications for binge-like eating behavior. Physiology & Behavior, 260, 114069.
  Faesel, Nadine; Koch, Michael & Fendt, Markus