id_993. FUNCTIONAL INTERACTION OF 5-HT7 AND NMDA RECEPTORS IN STRESS-INDUCED BEHAVIORAL AND SYNAPTIC ALTERATIONS
Zeinab Bedrood1, Monika Bijata1, Izabela Figiel1, Kim Dore2, Bernadeta Szewczyk3, Jakub Wlodarczyk1
1 Nencki Institute of Experimental Biology, Laboratory of Cell Biophysics, 3 Pasteur St., Warsaw, Poland
2 University of California at San Diego, Center for Neural Circuits and Behavior, Department of Neuroscience and Section for Neurobiology, Division of Biology, California 92093, San Diego
3 Maj Institute of Pharmacology, Department of Neurobiology, Polish Academy of Sciences, 12 Smętna, Kraków, Poland
INTRODUCTION: Major depressive disorder involves impaired synaptic plasticity and dysregulated serotonergic and glutamatergic signaling. Interactions between serotonin 5-HT7 receptors (5-HT7R) and N-methyl-D-aspartate receptors (NMDAR) may underlie stress-induced behavioral alterations; however, their direct interaction and functional relevance in stress-related pathology remain unclear.
AIM(S): To investigate physical and functional interactions between 5-HT7R and NMDAR and evaluate behavioral effects of pharmacological modulation in a treatment-resistant depression model.
METHOD(S): Receptor interactions were assessed in hippocampal neurons using co-localization analysis and fluorescence recovery after photobleaching (FRAP). Mice exposed to chronic immobilization stress combined with a zinc-deficient diet were treated with the NMDAR antagonist Nitrosynapsin or the multimodal antidepressant vortioxetine (VTX). Behavioral performance was evaluated using the tail suspension test (TST), novelty-suppressed feeding test (NSFT), and object location test (OLT).
RESULTS: Co-localization revealed substantial overlap between 5-HT7R and NMDAR. FRAP showed altered NMDA receptor mobility in neurons co-expressing 5-HT7R, indicating functional interaction. Nitrosynapsin reduced immobility and anxiety-like behavior to control levels. VTX decreased latency to feed in the NSFT and improved OLT performance, reversing stress-induced deficits.
CONCLUSIONS: These findings demonstrate spatial proximity and altered mobility of 5-HT7R and NMDAR in dendrites. Convergent behavioral effects of Nitrosynapsin and VTX suggest overlapping regulatory mechanisms underlying stress-induced neuronal dysfunction. Together, the receptors may act as a unified signaling module contributing to dendritic signaling associated with stress-related behavioral alterations.
FINANCIAL SUPPORT: This research was funded by the National Science Centre grant number 2021/41/B/NZ4/02603.