Interaction between 5-HT1A and 5-HT1B receptors: effects of 8-OH-DPAT-induced hypothermia in 5-HT1B receptor knockout mice

To test for adaptive compensatory changes that may have occurred in the: fu nctional activity of somatodendritic 5-HT1A receptors during the developmen t of constitutive "knockout" mice lacking the 5-HT1B receptor subtype (5-HT 1B -/- KO), we assayed for decrease in body temperature induced by an acute subcutaneous injection of the 5-HT1A receptor agonist, 8-hydroxy 2-di-n-pr opyl(amino)tetralin (8-OH-DPAT), either alone or in the presence of a selec tive 5-HT1A receptor antagonist, N-[4-(2-methoxyphenyl)-1-piperazinyl]-N-(2 -pyridinyl) cyclo-hexanecarboxamide (WAY 100635). We compared dose-response curves, time course study, calculated ED50 values (potency), maximal respo nse to 8-OH-DPAT (efficacy) as well as measurements of the dose-dependent b lockade of this response by WAY 100635 between wild-type controls and mutan t mice. We found a higher efficacy of 8-OH-DPAT-induced hypothermia in 5-HT 1B -/- KO compared to wild-type mice suggesting that an adaptive thermoregu latory process involving the functional activity of somatodendritic 5-HT1A receptors is altered in mutant mice lacking 5-HT1B receptors. (C) 2001 Else vier Science B.V. All rights reserved.