The GR-FKBP51 interaction modulates fear memory but not spatial or recognition memory

Anlong Jiang; Chanjuan Zhou; James Samsom; Shuxin Yan; Dian Zheng Yu; Zheng-Ping Jia; Albert H C Wong; Fang Liu

doi:10.1016/j.pnpbp.2022.110604

The GR-FKBP51 interaction modulates fear memory but not spatial or recognition memory

Prog Neuropsychopharmacol Biol Psychiatry. 2022 Dec 20:119:110604. doi: 10.1016/j.pnpbp.2022.110604. Epub 2022 Jul 14.

Authors

Anlong Jiang¹, Chanjuan Zhou¹, James Samsom¹, Shuxin Yan¹, Dian Zheng Yu¹, Zheng-Ping Jia², Albert H C Wong³, Fang Liu⁴

Affiliations

¹ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada.
² Neurosciences & Mental Health, The Hospital for Sick Children, 555 University Ave., M5G 1X8, Toronto, Ontario, Canada.
³ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada; Department of Pharmacology, University of Toronto, Toronto, ON M5S 1A8, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada.
⁴ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: fang.liu@camh.ca.

PMID: 35839967
DOI: 10.1016/j.pnpbp.2022.110604

Abstract

The glucocorticoid receptor (GR) forms a protein complex with FKBP51 that is increased in post-traumatic stress disorder (PTSD) and by fear conditioned learning. Disrupting the GR-FKBP51 complex with a synthetic peptide can block the storage or retrieval of fear conditioned memories, which could be a novel approach to the alleviate fear associated memory in PTSD. However, a potential unacceptable side effect could be the impairment of other types of memory. Thus, we investigated the effect of disrupting the GR-FKBP51 complex on recognition memory using the novel object and displaced object recognition tasks, spatial memory in the Morris water maze, and on social interaction in Crawley's three-chamber social interaction test. We did not observe adverse effects on these other types of memory and conclude that the GR-FKBP51 interaction remains a promising target for treating psychiatric disorders characterized by unwanted aversive memories such as in PTSD.

Keywords: Anti-aversive effects; Cognitive functions; FKBP51; Glucocorticoid receptor; Protein complex.

MeSH terms

Fear
Humans
Receptors, Glucocorticoid* / metabolism
Recognition, Psychology*
Stress Disorders, Post-Traumatic* / drug therapy
Stress Disorders, Post-Traumatic* / metabolism
Tacrolimus Binding Proteins* / metabolism

Substances

Receptors, Glucocorticoid
Tacrolimus Binding Proteins
tacrolimus binding protein 5