5-HT1B receptor knockout mice show no adaptive changes in 5-HT1A receptor function as measured telemetrically on body temperature and heart rate responses

Two presynaptic receptors play an important role in the regulation of serotonergic neurotransmission, i.e., the 5-HT1A and 5-HT1B receptor. The present study focuses on putative adaptive changes in the 5-HT1A receptor system in mice that lack 5-HT1B receptors (5-HT1B KO). 5-HT1A receptor sensitivity was assessed in vivo in two models of presynaptic 5HT(1)A receptor activity: agonist-induced hypothermia and prevention of stress-induced hyperthermia. The effects of 5-HT1A receptor activation by flesinoxan (0.1-3.0 mg/kg s.c.) were determined telemetrically on body temperature and heart rate in 5-HT1B KO and wild-type (WT) mice. Flesinoxan induced hypothermia dose-dependently without affecting heart rate and prevented stress-induced hyperthermia and tachycardia equipotently in both genotypes. Specificity of these responses was confirmed by blockade with the selective 5-HT1A receptor antagonist WAY100635 (1.0 mg/kg s.c.). The importance of continuous sampling in freely moving subjects to improve appropriate characterization of mutants is discussed. 5-HT1B KO mice showed no shift in 5-HT1A receptor sensitivity compared to WT mice. This study found no indications for adaptive changes in presynaptic 5-HT1A receptor function in 5-HT1B KO mice as measured telemetrically on body temperature and heart rate responses. (C) 2002 Elsevier Science Inc.