ANXIOLYTIC EFFECTS OF FLESINOXAN IN THE STRESS-INDUCED HYPERTHERMIA PARADIGM IN SINGLY-HOUSED MICE ARE 5-HT1A RECEPTOR-MEDIATED

In the stress-induced hyperthermia paradigm in singly-housed male mice , two sequential rectal temperature measurements reveal the basal temp erature (T-1) and, 10 min later, an enhanced body temperature (T-2), d ue to the stress of the first rectal measurement. The difference T-2-T -1 (Delta T) is the stress-induced hyperthermia and putatively reflect s a stress-induced anxiogenic response. The full 5-HT1A receptor agoni st flesinoxan ((+)-enantiomer), its (-)-enantiomer and the racemic mix ture reduced stress-induced hyperthermia effects, indicating putative anxiolytic properties. The ratio of their potencies to reduce stress-i nduced hyperthermia was similar to their potency in receptor binding a ffinities for 5-HT1A receptors, supporting that the anti-hyperthermia effects are mediated by the 5-HT1A receptor. This was further substant iated when the 5-HT1A receptor antagonists WAY 100635 ethoxyphenyl)-1- piperazinyl]ethyl]-N-(2-pyridinyl) cyclo-hexane carboxamine trihydroch loride) and DU 125530 -[4-(7-chloro-2,3-dihydro-1,4-benzodioxin-5-yl)- 1- l]butyl]-1,2-benzisothiazol-3(2H)-one-1,1-dioxide, monomesylate) bo th were able to antagonize the anti-stress-induced hyper thermia effec ts of flesinoxan. The stress-induced hyperthermia paradigm in singly-h oused mice represents a simple and robust paradigm to measure putative anxiolytic effects of drugs. (C) 1998 Elsevier Science B.V.