Central 5-HT3 receptor-induced hypothermia in mice: interstrain differences and comparison with hypothermia mediated via 5-HT1A receptor.
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.
Naumenko
Vladimir S
VS
Department of Behavioral Neurogenomics, Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Science, Lavrentieva av. 10, Novosibirsk 630090, Russia. naumenko2002@bionet.nsc.ru
Kondaurova
Elena M
EM
Popova
Nina K
NK
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001645:Biguanides / Q000008:administration & dosage / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007035:Hypothermia / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D017294:Ondansetron / Q000008:administration & dosage / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism; D058829:Serotonin 5-HT1 Receptor Antagonists; D058827:Serotonin 5-HT3 Receptor Agonists; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology; D013045:Species Specificity
D000631:Aminopyridines; D001645:Biguanides; D010879:Piperazines; D044406:Receptors, Serotonin, 5-HT3; D058829:Serotonin 5-HT1 Receptor Antagonists; D058827:Serotonin 5-HT3 Receptor Agonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; C087205:4-(2'-methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-iodobenzamido)ethyl)piperazine; D017294:Ondansetron; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C065734:1-(3-chlorophenyl)biguanide