interstrain differences 5-HT3, receptor central-induced hypothermia and comparison with hypotermia mediated via 5-HT 1A receptor
The selective agonist of 5-HT3 receptors 1-(3-Chlorophenyl)biguanide hydrochloride (m-CPBG) administered intraventricularly (40, 80 or 160 nmol) produced distinct hypothermic response in AKR/2J mice. At the same time, intraperitoneal administration of m-CPBG in wide dose ranges (0.5, 1.0, 5.0 or 10.0 mg/kg) caused no effect on the body temperature. These fi ndings suggest: (1) the implication of central, rather than peripheral 5-HT3 receptor in thermoregulation; (2) the inability of m-CPBG to permeate through blood-brain barrier in mice. The comparison of brain 5-HT3-induced hypothermic reaction between six inbred mouse strains (DBA/2J, CBA/Lac, C57BL/6, BALB/c, ICR, AKR/J) was performed and two highly sensitive to m-CPBG mouse strains (CBA/Lac and C57BL/6) were found.In aforenamed six inbred mouse strains the functional activity of 5-HT1A receptors was studied. Considerable interstrain differences were found in the intensity of hypothermic response produced by intraperitoneal administration of selective agonist of 5-HT1A receptors – 8-OHDPAT. The comparison of hypothermic reaction induced by central administration of m-CPBG and hypothermia produced by 8-OH-DPAT revealed signifi cant correlation between 5-HT3 and 5-HT1A-induced hypothermia in fi ve out of six investigated inbred mouse strains. The data suggest the association of the brain 5-HT3 and 5-HT1A receptors in the mechanisms of serotonin-conditioned hypothermia.