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 journalArticlepeer-review

8 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

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry

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