Central 5-HT3 receptor-induced hypothermia in mice: interstrain differences and comparison with hypothermia mediated via 5-HT1A receptor.

Abstract

The selective agonist of serotonin 5-HT(3) receptor 1-(3-chlorophenyl)biguanide hydrochloride (m-CPBG) administered intracerebroventricularly (40, 80 or 160 nmol) produced long-lasting dose-dependent hypothermic response in AKR/2J mice. m-CPBG (160 nmol i.c.v.) induced profound hypothermia (delta t=-4 degrees C) that lasted up to 7 h. m-CPBG (40 nmol i.c.v.)-induced hypothermia was attenuated by 5-HT(3) receptor antagonist ondansetron pretreatment. At the same time, intraperitoneal administration of m-CPBG in a wide range of doses (0.5, 1.0, 5.0 or 10.0 mg/kg) did not affect the body temperature. These findings indicate: (1) the implication of central, rather than peripheral 5-HT(3) receptor in the thermoregulation; (2) the inability of m-CPBG to cross blood-brain barrier in mice. The comparison of brain 5-HT(3)-induced hypothermic reaction in six inbred mouse strains (DBA/2J, CBA/Lac, C57BL/6, BALB/c, ICR, AKR/J) was performed and two highly sensitive to m-CPBG strains (CBA/Lac and C57BL/6) were found. In the same six mouse strains the functional activity of 5-HT(1A) receptor was studied. The comparison of hypothermic reactions produced by 5-HT(1A) receptor agonist 8-OH-DPAT (1.0 mg/kg i.p.) and m-CPBG revealed significant correlation between 5-HT(3) and 5-HT(1A)-induced hypothermia in five out of six investigated mouse strains. 5-HT(1A) receptor antagonist p-MPPI pretreatment (1 mg/kg i.p.) diminished hypothermia produced by centrally administered m-CPBG (40 nmol i.c.v.). The data suggest the cross-talk between 5-HT(1A) and 5-HT(3) receptors in the mechanism of 5-HT-related hypothermia.

• Authors: Vladimir S Naumenko, Elena M Kondaurova, Nina K Popova
• Journal: Neuroscience letters (Neurosci Lett) Vol. 465 Issue 1 Pg. 50-4 (Nov 06 2009) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 19735696 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aminopyridines
• Biguanides
• Piperazines
• Receptors, Serotonin, 5-HT3
• Serotonin 5-HT1 Receptor Antagonists
• Serotonin 5-HT3 Receptor Agonists
• Serotonin Antagonists
• Serotonin Receptor Agonists
• Receptor, Serotonin, 5-HT1A
• 4-(2'-methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-iodobenzamido)ethyl)piperazine
• Ondansetron
• 8-Hydroxy-2-(di-n-propylamino)tetralin
• 1-(3-chlorophenyl)biguanide

Topics

• 8-Hydroxy-2-(di-n-propylamino)tetralin (pharmacology)
• Aminopyridines (pharmacology)
• Animals
• Biguanides (administration & dosage, pharmacology)
• Blood-Brain Barrier (drug effects)
• Body Temperature (drug effects)
• Dose-Response Relationship, Drug
• Hypothermia (chemically induced, physiopathology)
• Male
• Mice
• Mice, Inbred Strains
• Ondansetron (administration & dosage, pharmacology)
• Piperazines (pharmacology)
• Receptor, Serotonin, 5-HT1A (metabolism)
• Receptors, Serotonin, 5-HT3 (metabolism)
• Serotonin 5-HT1 Receptor Antagonists
• Serotonin 5-HT3 Receptor Agonists
• Serotonin Antagonists (administration & dosage, pharmacology)
• Serotonin Receptor Agonists (administration & dosage, pharmacology)
• Species Specificity