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

4 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry

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