Stress-induced hyperthermia is reduced by rapid-acting anxiolytic drugs independent of injection stress in rats

Christiaan H Vinkers, Noëlle M de Jong, Cor J Kalkman, Koen G C Westphal, Ruud van Oorschot, Berend Olivier, S Mechiel Korte, Lucianne Groenink

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21 Citations (Scopus)


BACKGROUND: Stress-induced hyperthermia (SIH) is the transient rise in body temperature after encountering a stressor. The SIH response can be blocked by administration of various anxiolytic drugs prior to inducing stress. However, a drug injection involves handling and injection stress and therefore induces a SIH response itself. In the standard SIH test, drugs are therefore injected 60 min before stress induction to allow injection-induced hyperthermia to decline. This makes it difficult to study putative anxiolytic compounds with a short half-life. The present study therefore aimed to compare the effects of standard (stressful) and stress-free anxiolytic drug administration on the subsequent SIH response with a 10-minute injection-stressor interval.

METHODS: Anxiolytic drugs with short half-lives (midazolam, 8-OH-DPAT, nicotine) were injected subcutaneously in rats using either a stressful (manual injection) or stress-free injection (subcutaneous cannula) method 10 min before novel cage stress. Body temperature and locomotor activity were measured using telemetric transmitters.

RESULTS: Stressful and stress-free drug administration resulted in comparable drug effects on the stress-induced hyperthermia and locomotor responses in rats.

CONCLUSION: The present study shows that both stressful and stress-free drug injection shortly before a stressor results in reproducible attenuation of the SIH response in rats. In rats, a short injection-stressor interval can therefore be applied using the SIH model, enabling the study of putative anxiolytic drugs with short half-lives.

Original languageEnglish
Pages (from-to)413-8
Number of pages6
JournalPharmacology, biochemistry, and behavior
Issue number4
Publication statusPublished - Oct 2009
Externally publishedYes


  • 8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology
  • Animals
  • Anti-Anxiety Agents/therapeutic use
  • Body Temperature/drug effects
  • Drug Interactions
  • Fever/etiology
  • Injections, Intravenous/adverse effects
  • Male
  • Midazolam/therapeutic use
  • Motor Activity/drug effects
  • Nicotine/pharmacology
  • Nicotinic Agonists/pharmacology
  • Rats
  • Rats, Wistar
  • Serotonin 5-HT1 Receptor Agonists
  • Stress, Psychological/complications
  • Telemetry

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