The Effect of Propofol on a Forced Swim Test in Mice at 24 Hours

ABSTRACT: Background: There are few rapidly acting treatments for acute suicidality or treatment-resistant depression. Propofol (2,6-diisopropylphenol) is an intravenous anesthetic agent used in outpatient settings. It is a gamma-aminobutyric acid type A agonist and has affinity at the N-methyl-D-a...

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Main Authors: David G. Daniel, MD, Noah G. Daniel, Donald T. Daniel, Laura Copeland Flynn, MS, Michael H. Allen, MD
Format: Article
Language:English
Published: Elsevier 2020-01-01
Series:Current Therapeutic Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0011393X20300163
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author David G. Daniel, MD
Noah G. Daniel
Donald T. Daniel
Laura Copeland Flynn, MS
Michael H. Allen, MD
author_facet David G. Daniel, MD
Noah G. Daniel
Donald T. Daniel
Laura Copeland Flynn, MS
Michael H. Allen, MD
author_sort David G. Daniel, MD
collection DOAJ
description ABSTRACT: Background: There are few rapidly acting treatments for acute suicidality or treatment-resistant depression. Propofol (2,6-diisopropylphenol) is an intravenous anesthetic agent used in outpatient settings. It is a gamma-aminobutyric acid type A agonist and has affinity at the N-methyl-D-aspartate receptor. Elevation in mood and sociality in humans has been observed following propofol-induced anesthesia. Other authors reported an open-label study of repeated dosing of propofol in treatment-resistant depression in which several patients experienced sustained improvement. Recently, we reported that in a rodent model of despair, a forced swim test, 45 minutes after administration of 50 mg/kg propofol, immobility time was significantly reduced. Objective: The objective of the experiment was to determine whether the antidepressant-like effects of a single dose of propofol in mice are sustained for 24 hours. Methods: The time spent immobile during a forced swim test 24 hours after intraperitoneal administration of a single dose of propofol 50 mg/kg or 0.9% saline was evaluated in 24 adult male mice (C57/BL6). Immobility time was quantified and evaluated with a custom video analysis software program. Results: Propofol-treated mice were immobile for a mean (SEM) time of 115 (13) seconds, whereas saline-treated mice were immobile for a mean (SEM) time of 94 (14) seconds. A 2-tailed unpaired t test found no significant difference between the treatment groups (t = 1.07, df = 22; P = 0.30). Conclusions: Twenty-four hours after intraperitoneal administration, the effect of propofol on immobility time was not statistically significantly different from vehicle. However, given our previous report of at least a short-term benefit of propofol on struggling time in the forced swim time and an encouraging pilot study in humans with treatment-resistant depression, further evaluation of propofol's antidepressant potential may be warranted.
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spelling doaj.art-366602e60d57412fa1ebafbe007647ca2022-12-22T00:21:56ZengElsevierCurrent Therapeutic Research0011-393X2020-01-0192100590The Effect of Propofol on a Forced Swim Test in Mice at 24 HoursDavid G. Daniel, MD0Noah G. Daniel1Donald T. Daniel2Laura Copeland Flynn, MS3Michael H. Allen, MD4Bioniche Global Development, McLean, Virginia; Address correspondence to: David Daniel, Bioniche Global Development, PO Box 7137, McLean, VA 22106.Dartmouth College, Hanover, New HampshireBrown University, LLC, Providence, Rhode IslandLCF Consulting, LLC, Lake Forest, IllinoisUniversity of Colorado School of Medicine, Aurora, ColoradoABSTRACT: Background: There are few rapidly acting treatments for acute suicidality or treatment-resistant depression. Propofol (2,6-diisopropylphenol) is an intravenous anesthetic agent used in outpatient settings. It is a gamma-aminobutyric acid type A agonist and has affinity at the N-methyl-D-aspartate receptor. Elevation in mood and sociality in humans has been observed following propofol-induced anesthesia. Other authors reported an open-label study of repeated dosing of propofol in treatment-resistant depression in which several patients experienced sustained improvement. Recently, we reported that in a rodent model of despair, a forced swim test, 45 minutes after administration of 50 mg/kg propofol, immobility time was significantly reduced. Objective: The objective of the experiment was to determine whether the antidepressant-like effects of a single dose of propofol in mice are sustained for 24 hours. Methods: The time spent immobile during a forced swim test 24 hours after intraperitoneal administration of a single dose of propofol 50 mg/kg or 0.9% saline was evaluated in 24 adult male mice (C57/BL6). Immobility time was quantified and evaluated with a custom video analysis software program. Results: Propofol-treated mice were immobile for a mean (SEM) time of 115 (13) seconds, whereas saline-treated mice were immobile for a mean (SEM) time of 94 (14) seconds. A 2-tailed unpaired t test found no significant difference between the treatment groups (t = 1.07, df = 22; P = 0.30). Conclusions: Twenty-four hours after intraperitoneal administration, the effect of propofol on immobility time was not statistically significantly different from vehicle. However, given our previous report of at least a short-term benefit of propofol on struggling time in the forced swim time and an encouraging pilot study in humans with treatment-resistant depression, further evaluation of propofol's antidepressant potential may be warranted.http://www.sciencedirect.com/science/article/pii/S0011393X20300163Depressionforced swim testGABApropofolsuicide
spellingShingle David G. Daniel, MD
Noah G. Daniel
Donald T. Daniel
Laura Copeland Flynn, MS
Michael H. Allen, MD
The Effect of Propofol on a Forced Swim Test in Mice at 24 Hours
Current Therapeutic Research
Depression
forced swim test
GABA
propofol
suicide
title The Effect of Propofol on a Forced Swim Test in Mice at 24 Hours
title_full The Effect of Propofol on a Forced Swim Test in Mice at 24 Hours
title_fullStr The Effect of Propofol on a Forced Swim Test in Mice at 24 Hours
title_full_unstemmed The Effect of Propofol on a Forced Swim Test in Mice at 24 Hours
title_short The Effect of Propofol on a Forced Swim Test in Mice at 24 Hours
title_sort effect of propofol on a forced swim test in mice at 24 hours
topic Depression
forced swim test
GABA
propofol
suicide
url http://www.sciencedirect.com/science/article/pii/S0011393X20300163
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