The Effect of Acutely Administered Propofol on Forced Swim Test Outcomes in Mice

Objective: Propofol (2,6-diisopropylphenol) is a gamma-aminobutyric acid type A agonist intravenous anesthetic agent used in outpatient settings. Based on anecdotal reports of improved mood in humans following propofol-induced anesthesia, the impact of acute propofol treatment alone or in combination with subchronic fluoxetine dosing was tested on forced swim test (FST) performance. Design: Seventy-two adult male mice (C57/BL6, CRL-provided) were pretreated daily with saline or fluoxetine (20 mg/kg, intraperitoneally) (21 days for cohort 1; 24 days for cohort 2). At 24 hours after the last pretreatment injection, the mice received saline or propofol (35 or 50 mg/kg, intraperitoneally). Then, 45 minutes later, the mice underwent a five-minute FST. Immobility time was quantified and evaluated with a custom video-analysis software program. Results: A one-way analysis of variance indicated statistically significant effects of propofol on immobility time in cohorts 1 and 2. A comparison performed using Dunnett's method revealed that propofol 50 mg/kg (p < 0.05) but not 35 mg/kg (p = not significant) reduced immobility time as compared with in the saline-saline control group (difference between means of 38.42 and 16.46 seconds, respectively). Conclusion: In comparison with saline, propofol significantly decreased immobility time during the FST, which models depression and resilience to stress. Our preclinical results are consistent with a small open-label study of propofol used in treatment-resistant depression recently reported by Mickey BJ, White AT, Arp AM, et al (2018). Further investigation of propofol regarding its potential antidepressant effects seems warranted.