Sigma-1 Receptor Activation by Fluvoxamine Ameliorates ER Stress, Synaptic Dysfunction and Behavioral Deficits in a Ketamine Model of Schizophrenia.
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology July 25, 2025 Mariam K Ahmed, Kareem Abdou, Weam W Ibrahim et al. 5 citations
Fluvoxamine, a sigma-1 receptor agonist, alleviated learning deficits, cognitive inflexibility, and social impairments in a rat model of schizophrenia induced by ketamine. It restored nNOS/PSD-95/NMDAR signaling, increased parvalbumin and GAD67 levels in the prefrontal cortex, and reduced markers of unfolded protein response (IRE-1, PERK, ATF-6), indicating relief from ER stress. Fluvoxamine also lowered inflammatory markers (Iba-1, TNF-α) and apoptotic markers (Bax, caspase-12) while increasing Bcl-2, and reduced neuronal damage. Co-administration of the sigma-1 receptor blocker NE100 diminished these effects, implicating sigma-1 receptor signaling as a therapeutic target for schizophrenia.