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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 7 days to an incubator (23 °C, 15 min), then exposed, 24 h 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 (5 mg/kg, s.c., 23 h, 5 h, and 1 h 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.

Original languageEnglish (US)
Pages (from-to)162-168
Number of pages7
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume79
DOIs
StatePublished - Oct 3 2017
Externally publishedYes

Fingerprint

Citalopram
Antidepressive Agents
Fever
Major Depressive Disorder
Body Temperature
Incubators
Controlled Clinical Trials
Serotonin Uptake Inhibitors
Wistar Rats
Rodentia
Therapeutics
Placebos
Temperature

Keywords

  • Alternative
  • Antidepressant
  • Complementary
  • Integrative health care
  • Serotonin
  • Whole-body heating

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry

Cite this

Whole-body hyperthermia and a subthreshold dose of citalopram act synergistically to induce antidepressant-like behavioral responses in adolescent rats. / Hale, Matthew W.; Lukkes, Jodi L.; Dady, Kathleen F.; Kelly, Kyle J.; Paul, Evan D.; Smith, David G.; Raison, Charles L; Lowry, Christopher A.

In: Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 79, 03.10.2017, p. 162-168.

Research output: Contribution to journalArticle

Hale, Matthew W. ; Lukkes, Jodi L. ; Dady, Kathleen F. ; Kelly, Kyle J. ; Paul, Evan D. ; Smith, David G. ; Raison, Charles L ; Lowry, Christopher A. / Whole-body hyperthermia and a subthreshold dose of citalopram act synergistically to induce antidepressant-like behavioral responses in adolescent rats. In: Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2017 ; Vol. 79. pp. 162-168.
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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 7 days to an incubator (23 °C, 15 min), then exposed, 24 h 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 (5 mg/kg, s.c., 23 h, 5 h, and 1 h 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.",
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AU - Hale, Matthew W.

AU - Lukkes, Jodi L.

AU - Dady, Kathleen F.

AU - Kelly, Kyle J.

AU - Paul, Evan D.

AU - Smith, David G.

AU - Raison, Charles L

AU - Lowry, Christopher A.

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N2 - 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 7 days to an incubator (23 °C, 15 min), then exposed, 24 h 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 (5 mg/kg, s.c., 23 h, 5 h, and 1 h 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.

AB - 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 7 days to an incubator (23 °C, 15 min), then exposed, 24 h 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 (5 mg/kg, s.c., 23 h, 5 h, and 1 h 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.

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