Disrupting the α7nAChR–NR2A protein complex exerts antidepressant-like effects

Molecular Brain

Anlong Jiang¹  Ping Su¹  Shupeng Li¹  Albert H. C. Wong²  Fang Liu³ 

[1] Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, M5T 1R8, Toronto, ON, Canada;Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, M5T 1R8, Toronto, ON, Canada;Departments of Pharmacology, University of Toronto, M5T 1R8, Toronto, ON, Canada;Institutes of Medical Science, University of Toronto, M5T 1R8, Toronto, ON, Canada;Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, M5T 1R8, Toronto, ON, Canada;Institutes of Medical Science, University of Toronto, M5T 1R8, Toronto, ON, Canada;University of Toronto, M5T 1R8, Toronto, ON, Canada;University of Toronto, M5T 1R8, Toronto, ON, Canada;

关键词: α7 Nicotinic acetylcholine receptor (α7nAChR);    Extracellular signal-regulated kinase (ERK);    Forced swim test (FST);    Major depressive disorder (MDD);    NMDA glutamate receptors (NMDARs);   

DOI  :  10.1186/s13041-021-00817-3

来源: Springer

【 摘 要 】

Major depressive disorder (MDD) is associated with significant morbidity and mortality. Most antidepressant medications target the serotonin and norepinephrine transporters, but a significant minority of patients do not respond to treatment and novel therapeutic targets are needed. We previously identified a protein complex composed of the α7 nicotinic acetylcholine receptor (nAChR) and NMDA glutamate receptors (NMDARs), through which α7nAChR upregulates NMDAR function. Disruption of the α7nAChR–NMDAR complex with an interfering peptide blocked α7nAChR-mediated upregulation of NMDAR function and cue-induced reinstatement of nicotine seeking in rat models of relapse. Here we report that disrupting the α7nAChR–NMDAR complex with the interfering peptide also has antidepressant-like effects in the forced swim test (FST), a common rat behaviour screening test for antidepressant effects. Furthermore, the interfering peptide significantly increases extracellular signal-regulated kinase (ERK) activity in the animals subjected to the FST. Our results provide a novel potential therapeutic target for the development of new antidepressant medications.

【 授权许可】

CC BY