['Sigma-1 receptors are involved in the pathophysiological process of several neuropsychiatric diseases such as epilepsy, depression. Allosteric modulation represents an important mechanism for receptor functional regulation. In this study, we examined antidepressant activity of the latest identified novel and selective allosteric modulator of sigma-1 receptor 3-methyl-phenyl-2, 3, 4, 5-tetrahydro-1H-benzo[d]azepin-7-ol (SOMCL-668).', 'A single administration of SOMCL-668 decreased the immobility time in the forced swimming test (FST) and tailing suspended test in mice, which were abolished by pretreatment of sigma-1 receptor antagonist BD1047. In the chronic unpredicted mild stress (CUMS) model, chronic application of SOMCL-668 rapidly ameliorated anhedonia-like behavior (within a week), accompanying with the enhanced expression of brain-derived neurotrophic factor (BDNF) and phosphorylation of glycogen synthase kinase 3β (GSK3β) (Ser-9) in the hippocampus. SOMCL-668 also rapidly promoted the phosphorylation of GSK3β (Ser-9) in an allosteric manner in vitro. In the cultured primary neurons, SOMCL-668 enhanced the sigma-1 receptor agonist-induced neurite outgrowth and the secretion of BDNF.'] Does allosteric Modulation of Sigma-1 Receptors elicit Rapid Antidepressant Activity?