Whole-body hyperthermia and a subthreshold dose of citalopram act synergistically to induce antidepressant-like behavioral responses in adolescent rats

Matthew W Hale; Jodi L Lukkes; Kathleen F Dady; Kyle J Kelly; Evan D Paul; David G Smith; Charles L Raison; Christopher A Lowry

doi:10.1016/j.pnpbp.2017.06.006

Whole-body hyperthermia and a subthreshold dose of citalopram act synergistically to induce antidepressant-like behavioral responses in adolescent rats

Prog Neuropsychopharmacol Biol Psychiatry. 2017 Oct 3;79(Pt B):162-168. doi: 10.1016/j.pnpbp.2017.06.006. Epub 2017 Jun 12.

Authors

Matthew W Hale¹, Jodi L Lukkes², Kathleen F Dady², Kyle J Kelly², Evan D Paul², David G Smith³, Charles L Raison⁴, Christopher A Lowry⁵

Affiliations

¹ Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA; School of Psychology and Public Health, La Trobe University, Melbourne, VIC 3086, Australia.
² Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
³ Department of Chemistry and Biochemistry, University of Colorado Boulder, Boulder, CO 80309, USA.
⁴ Human Development and Family Studies, School of Human Ecology, University of Wisconsin-Madison, WI 53706, USA; Department of Psychiatry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA.
⁵ Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA; Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA; Department of Physical Medicine and Rehabilitation, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Center for Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Rocky Mountain Mental Illness Research, Education and Clinical Center, Denver, CO 80220, USA; Military and Veteran Microbiome Consortium for Research and Education (MVM-CoRE), Aurora, CO 80045, USA. Electronic address: christopher.lowry@colorado.edu.

PMID: 28619470
DOI: 10.1016/j.pnpbp.2017.06.006

Abstract

Background: Open and randomized, double blind, placebo-controlled clinical trials have demonstrated clinical efficacy of infrared whole-body hyperthermia in treatment of major depressive disorder (MDD). Demonstration of antidepressant-like behavioral effects of whole-body hyperthermia in preclinical rodent models would provide further support for the clinical use of infrared whole-body hyperthermia for the treatment of MDD, and would provide additional opportunities to explore underlying mechanisms.

Methods: Adolescent male Wistar rats were habituated daily for 7days to an incubator (23°C, 15min), then exposed, 24h later, to an 85-min period of whole-body hyperthermia (37°C) or control conditions (23°C), with or without pretreatment with a subthreshold dose of the selective serotonin reuptake inhibitor, citalopram (5mg/kg, s.c., 23h, 5h, and 1h before behavioral testing in a 5-min forced swim test). Rectal temperature was monitored daily and immediately before and after the forced swim test to determine the relationship between body temperature and antidepressant-like behavioral responses.

Results: Whole-body hyperthermia and citalopram independently increased body temperature and acted synergistically to induce antidepressant-like behavioral responses, as measured by increased swimming and decreased immobility in the absence of any effect on climbing behaviors in the forced swim test, consistent with a serotonergic mechanism of action.

Conclusions: Preclinical data support use of infrared whole-body hyperthermia in the treatment of MDD.

Keywords: Alternative; Antidepressant; Complementary; Integrative health care; Serotonin; Whole-body heating.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't

MeSH terms

Analysis of Variance
Animals
Antidepressive Agents / pharmacology*
Body Temperature / drug effects
Body Weight / drug effects
Citalopram / pharmacology*
Depressive Disorder, Major / physiopathology
Depressive Disorder, Major / therapy*
Disease Models, Animal
Hyperthermia, Induced*
Male
Rats, Wistar
Rectum
Selective Serotonin Reuptake Inhibitors / pharmacology*

Substances

Antidepressive Agents
Serotonin Uptake Inhibitors
Citalopram