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Central 5-HT3 Receptor-Induced Hypothermia in Mice: Interstrain Differences and Comparison With Hypothermia Mediated via 5-HT1A Receptor

Central 5-HT3 Receptor-Induced Hypothermia in Mice: Interstrain Differences and Comparison With Hypothermia Mediated via 5-HT1A Receptor

Vladimir S Naumenko, Elena M Kondaurova, Nina K Popova

Neurosci Lett. 2009 Nov 6;465(1):50-4.

PMID: 19735696

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP2113055	1-(3-Chlorophenyl)biguanide hydrochloride		2113-05-5	Price

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