The combination of citalopram and crocin synergistically alleviates the anxiogenic-related behaviors induced by acute restraint stress (ARS) in male mice.

Citalopram, a selective serotonin reuptake inhibitor (SSRI), is well-known for the treatment of mood disorders and generalized anxiety disorder. Furthermore, crocin caused antidepressant impacts in clinical research and extensive anxiolytic impacts in experimental animal models. This research was designed to assess the effects of drug combinations of citalopram and crocin on anxiety-related behaviors induced by acute restraint stress (ARS) and aimed to discover the type of interaction between components. Acute restraint stress (ARS) was conducted by movement restraint for 4 hours. Anxiety-related behaviors were evaluated by elevated plus-maze (EPM). The results showed that induction of acute stress for 4 hours decreased the percent of open arm time (%OAT) and the percent of open arm entry (%OAE), showing anxiogenic-related behaviors. Intraperitoneal (i.p.) administration of citalopram (2 and 4 mg/kg) or crocin (40 mg/kg) induced anxiolytic-related behaviors in non-acute restraint stress (NARS) and ARS mice due to the enhancement of %OAT and %OAE. Additionally, i.p. co-injection of a sub-threshold dosage of citalopram (1 mg/kg) along with different dosages of crocin (10, 20, and 40 mg/kg) induced anxiolytic-related behaviors through augmentation of %OAT and %OAE. None of the above dosages of drugs changed the locomotor activity. Moreover, our results displayed a synergistic effect between citalopram and crocin on inducing anxiolytic-related behaviors in male mice. Our findings suggest that citalopram and crocin interact with each other for modulation of anxiety-related behaviors in the NARS and ARS mice.