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

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. 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. 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). 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.