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


CONCLUSIONS
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.
Vinkers
Christiaan H
CH
Dept. of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS) Utrecht University, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands. c.h.vinkers@uu.nl
de Jong
Noëlle M
NM
Kalkman
Cor J
CJ
Westphal
Koen G C
KG
van Oorschot
Ruud
R
Olivier
Berend
B
Korte
S Mechiel
SM
Groenink
Lucianne
L
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001831:Body Temperature / Q000187:drug effects; D004347:Drug Interactions; D005334:Fever / Q000209:etiology* / Q000517:prevention & control*; D007275:Injections, Intravenous / Q000009:adverse effects*; D008297:Male; D008874:Midazolam / Q000627:therapeutic use; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D058825:Serotonin 5-HT1 Receptor Agonists; D013315:Stress, Psychological / Q000150:complications* / Q000517:prevention & control*; D013686:Telemetry
D014151:Anti-Anxiety Agents; D018722:Nicotinic Agonists; D058825:Serotonin 5-HT1 Receptor Agonists; D009538:Nicotine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D008874:Midazolam