STRESS-INDUCED HYPERTHERMIA AS A PUTATIVE ANXIETY MODEL

In group-housed mice (ten per cage), mice removed last from their home cage always have higher rectal temperatures than mice removed first f rom this cage. Stress-induced hyperthermia is calculated as the differ ence (Delta T) between the basal temperature (mouse number 1) and the end temperature (mouse number 10) when the temperature of the ten mice is sequentially measured using a 1-min interval between rectal measur ements. Using this protocol, various drugs, belonging to different pha rmacological classes, were tested in order to investigate their putati ve anxiolytic effect, measured as a decrease in Delta T. Benzodiazepin es (diazepam, alprazolam), alcohol, and some (flesinoxan, buspirone), but not all(ipsapirone) 5-HT1A receptor agonists had anxiolytic proper ties with this protocol. Clonidine (alpha(2)-adrenoceptor agonist) and prazosine (alpha(1)-adrenoceptor antagonist) had, but at high doses, some anxiolytic actions. Antidepressants (desipramine, fluvoxamine, no mifensine, tianeptine, amitriptyline, clomipramine, imipramine), serot onergic ligands (ondansetron, ketanserin, 1-(2,5-dimethoxy-4-iodopheny l)-2-aminopropane (DOI), fenfluramine, metachlorophenylpiperazine (mCP P), eitoprazine) and various other drugs (phenobarbital, pentetrazol, haloperidol, apomorphine, amphetamine, (+)-N-[1-methyl-2-oxo-5-phenyl- 2,3-dihydro yl]-N'-(3-methylphenyl)urea (MSD 365260), dizocilpine and acetyl salicylic acid) had no anxiolytic activity. The stress-induced hyperthermia protocol used was unable to detect anxiogenic properties of drugs, probably due to a (physiological) ceiling in the maximal end temperature. The stress-induced hyperthermia protocol with mice can b e used to measure anxiolytic properties of drugs and is a fast and rob ust model which does not need extensive training of animals.