Anxiolytic effects of flesinoxan in the stress-induced hyperthermia paradigm in singly-housed mice are 5-HT1A receptor mediated

European Journal of Pharmacology
Berend OlivierJ van der Heyden

Abstract

In the stress-induced hyperthermia paradigm in singly-housed male mice, two sequential rectal temperature measurements reveal the basal temperature (T1) and, 10 min later, an enhanced body temperature (T2), due to the stress of the first rectal measurement. The difference T2 - T1 (deltaT) is the stress-induced hyperthermia and putatively reflects a stress-induced anxiogenic response. The full 5-HT1A receptor agonist flesinoxan ((+)-enantiomer), its (-)-enantiomer and the racemic mixture reduced stress-induced hyperthermia effects, indicating putative anxiolytic properties. The ratio of their potencies to reduce stress-induced hyperthermia was similar to their potency in receptor binding affinities for 5-HT1A receptors, supporting that the anti-hyperthermia effects are mediated by the 5-HT1A receptor. This was further substantiated when the 5-HT1A receptor antagonists WAY 100635 ((N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclo-hexane carboxamine trihydrochloride) and DU 125530 (2-[4-[4-(7-chloro-2,3-dihydro-1,4-benzodioxin-5-yl)-1-piperazinyl ]butyl]-1,2-benzisothiazol-3(2H)-one-1,1-dioxide, monomesylate) both were able to antagonize the anti-stress-induced hyperthermia effects of flesinoxan. The stress-ind...Continue Reading

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Citations

Apr 12, 2001·Biological Psychiatry·T PattijB Olivier
Jul 29, 2000·European Journal of Pharmacology·J A BouwknechtB Olivier
Feb 26, 2003·European Journal of Pharmacology·Berend OlivierLucianne Groenink
Mar 26, 2003·Journal of Psychiatric Research·Xiaoqing LiuHoward K Gershenfeld
Mar 19, 2002·Physiology & Behavior·Hitomi AkutsuYuji Mori
Mar 20, 2002·Pharmacology, Biochemistry, and Behavior·Berend OlivierTheo J J Zethof
Oct 16, 1999·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·N HaddjeriP Blier
Dec 11, 2002·The European Journal of Neuroscience·J BrodkinM A Varney
Dec 14, 2001·Behavioural Pharmacology·B OlivierM Toth
Mar 2, 2006·Genes, Brain, and Behavior·M J V van BogaertB Olivier
Apr 9, 2008·Behavioural Brain Research·Sven Ove OgrenOliver Stiedl
May 21, 2011·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·George S Zubenko, Hugh B Hughes
Jul 29, 2008·Progress in Brain Research·Janet A AmicoRegis R Vollmer
Apr 19, 2008·European Journal of Pharmacology·Christiaan H VinkersLucianne Groenink
Oct 27, 2004·Pharmacology, Biochemistry, and Behavior·Si Wei ChenYi Jing Zhang
May 11, 2002·Journal of Biological Rhythms·Elizabeth PelosoEvelyn Satinoff
Jun 14, 2020·Psychopharmacology·Danielle J HouwingJocelien D A Olivier
Dec 17, 2009·European Journal of Pharmacology·Jocelien D A OlivierBart A Ellenbroek

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