Depression, affecting 280 million people worldwide, is marked by a significant treatment gap. Current therapies with delayed onset of action fail to alleviate the symptoms in almost half of patients, often neglecting the cognitive deficits. This highlights the critical need for fast-acting antidepressants with memory-enhancing properties. HBK-15, a multimodal compound, previously demonstrated antidepressant-, anxiolytic-like and antiamnesic effects in rodents. Our study aimed to explore HBK-15's potential in reversing stress-induced behavioral abnormalities and elucidating its underlying mechanisms. We utilized a mouse model of unpredictable chronic mild stress, along the sucrose preference test and novel object recognition test as behavioral endpoints. Additionally, we measured levels of various proteins in the prefrontal cortex to understand the molecular changes caused by HBK-15. To validate whether the pharmacological effects were BDNF-dependent, we used mice with BDNF Val66Met polymorphism. Finally, we repeated behavioral experiments inhibiting ERK1/2 phosphorylation. We discovered that a single administration of HBK-15 reversed decreased sucrose preference and novel object exploration time in stressed mice, and these effects lasted for 24 hours. HBK-15 also increased levels of certain proteins in the prefrontal cortex of stressed animals, including BDNF, pCaMKIV, pPKA, pRSK2, and pERK1/2. Interestingly, HBK-15's antidepressant-like effect may not depend on BDNF release in contrast to the antiamnesic activity. However, both antidepressant-like and antiamnesic effects of HBK-15 rely on ERK1/2 phosphorylation in the prefrontal cortex. These findings propose HBK-15 and similar compounds as promising treatments for depression with cognitive impairments. This study was supported by National Science Centre (2019/34/E/NZ7/00454, 2017/01/X/NZ7/00818) and JUMC grants.