5-HT(1B) receptor knockout mice show no adaptive changes in 5-HT(1A) 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-HT(1A) and 5-HT(1B) receptor. The present study focuses on putative adaptive changes in the 5-HT(1A) receptor system in mice that lack 5-HT(1B) receptors (5-HT(1B) KO). 5-HT(1A) receptor sensitivity was assessed in vivo in two models of presynaptic 5-HT(1A) receptor activity: agonist-induced hypothermia and prevention of stress-induced hyperthermia. The effects of 5-HT(1A) receptor activation by flesinoxan (0.1-3.0 mg/kg s.c.) were determined telemetrically on body temperature and heart rate in 5-HT(1B) 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-HT(1A) 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-HT(1B) KO mice showed no shift in 5-HT(1A) receptor sensitivity compared to WT mice. This study found no indications for adaptive changes in presynaptic 5-HT(1A) receptor function in 5-HT(1B) KO mice as measured telemetrically on body temperature and heart rate responses.
Bouwknecht
J Adriaan
JA
Department of Psychopharmacology, Faculty of Pharmacy, Utrecht University, Utrecht, The Netherlands. ABouwknecht@bcm.tmc.edu
Hijzen
Theo H
TH
van der Gugten
Jan
J
Maes
Robert A A
RA
Hen
René
R
Olivier
Berend
B
D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000235:genetics*; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000172:deficiency* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000235:genetics* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013312:Stress, Physiological / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics*; D013686:Telemetry
D010879:Piperazines; D011725:Pyridines; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; C056895:flesinoxan; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide