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.

Abstract

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.

• Authors: J Adriaan Bouwknecht, Theo H Hijzen, Jan van der Gugten, Robert A A Maes, René Hen, Berend Olivier
• Journal: Brain research bulletin (Brain Res Bull) Vol. 57 Issue 1 Pg. 93-102 (Jan 01 2002) ISSN: 0361-9230 [Print] United States
• PMID: 11827741 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Piperazines
• Pyridines
• Receptor, Serotonin, 5-HT1B
• Receptors, Serotonin
• Receptors, Serotonin, 5-HT1
• Serotonin Antagonists
• Serotonin Receptor Agonists
• Serotonin
• flesinoxan
• N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide

Topics

• Adaptation, Physiological (genetics)
• Animals
• Body Temperature (drug effects, genetics)
• Central Nervous System (drug effects, metabolism, physiopathology)
• Heart Rate (drug effects, genetics)
• Male
• Mice
• Mice, Knockout
• Phenotype
• Piperazines (pharmacology)
• Pyridines (pharmacology)
• Receptor, Serotonin, 5-HT1B
• Receptors, Serotonin (deficiency, drug effects, genetics, metabolism)
• Receptors, Serotonin, 5-HT1
• Serotonin (genetics, metabolism)
• Serotonin Antagonists (pharmacology)
• Serotonin Receptor Agonists (pharmacology)
• Stress, Physiological (complications, metabolism, physiopathology)
• Synaptic Transmission (drug effects, genetics)
• Telemetry