Vortioxetine Reverses Impairment of Visuospatial Memory and Cognitive Flexibility Induced by Degarelix as a Model of Androgen Deprivation Therapy in Rats

Alexandra M. Vaiana, Amber M. Asher, Karla Tapia, David A. Morilak

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Androgen deprivation therapy (ADT) is a mainstay treatment for prostate cancer, but many patients experience cognitive impairment in domains mediated by the medial prefrontal cortex (mPFC) and hippocampus. Prostate cancer typically occurs in older patients (>65 years). As age is often accompanied by cognitive decline, it may impact the efficacy of any treatment aimed at restoring cognitive impairment induced by ADT. Vortioxetine, a multimodal antidepressant that improves cognition in depression, has been shown to be efficacious in elderly patients. Therefore, vortioxetine may improve cognition in older patients who experience cognitive decline after ADT. Methods: Young (3 months) and middle-aged (13 months) rats were used to investigate the influence of age on treating ADT-induced cognitive decline. As our previous studies used surgical castration, we tested if vortioxetine would reverse cognitive deficits associated with more translationally relevant chemical castration using degarelix. Vortioxetine was given in the diet for 21 days. Animals underwent behavioral testing to assess visuospatial memory mediated by the hippocampus and cognitive flexibility mediated by the mPFC. We also investigated changes in afferent-evoked responses in these regions in middle-aged rats. Results: Degarelix induced impairments in both visuospatial memory and cognitive flexibility that were reversed by vortioxetine. Vortioxetine also rescued afferent-evoked responses in the mPFC and hippocampus. However, modest age-related reductions in baseline visuospatial memory limited our ability to detect further decreases induced by degarelix in middle-aged rats due to a floor effect. Conclusion: These results suggest that vortioxetine may be a treatment option for older prostate cancer patients who experience cognitive decline after ADT.

Original languageEnglish (US)
Pages (from-to)279-290
Number of pages12
JournalNeuroendocrinology
Volume114
Issue number3
DOIs
StatePublished - Mar 1 2024

Keywords

  • Age
  • Cognition
  • Hippocampus
  • Novel object test
  • Prostate cancer
  • Testosterone

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

Fingerprint

Dive into the research topics of 'Vortioxetine Reverses Impairment of Visuospatial Memory and Cognitive Flexibility Induced by Degarelix as a Model of Androgen Deprivation Therapy in Rats'. Together they form a unique fingerprint.

Cite this