On the role of brain 5-HT7 receptor in the mechanism of hypothermia: comparison with hypothermia mediated via 5-HT1A and 5-HT3 receptor.

Abstract

Intracerebroventricular administration of selective agonist of serotonin 5-HT(7) receptor LP44 (4-[2-(methylthio)phenyl]-N-(1,2,3,4-tetrahydro-1-naphthalenyl)-1-pyperasinehexanamide hydrochloride; 10.3, 20.5 or 41.0 nmol) produced considerable hypothermic response in CBA/Lac mice. LP44-induced (20.5 nmol) hypothermia was significantly attenuated by the selective 5-HT(7) receptor antagonist SB 269970 (16.1 fmol, i.c.v.) pretreatment. At the same time, intraperitoneal administration of LP44 in a wide range of doses 1.0, 2.0 or 10.0 mg/kg (2.0, 4.0, 20.0 μmol/kg) did not cause considerable hypothermic response. These findings indicate the implication of central, rather than peripheral 5-HT(7) receptors in the regulation of hypothermia. The comparison of LP44-induced (20.5 nmol) hypothermic reaction in eight inbred mouse strains (DBA/2J, CBA/Lac, C57BL/6, BALB/c, ICR, AKR/J, C3H and Asn) was performed and a significant effect of genotype was found. In the same eight mouse strains, functional activity of 5-HT(1A) and 5-HT(3) receptors was studied. The comparison of hypothermic responses produced by 5-HT(7) receptor agonist LP44 (20.5 nmol, i.c.v.) and 5-HT(1A) receptor agonist 8-OH-DPAT 1.0 mg/kg, i.p. (3.0 μmol/kg), 5-HT(3) receptor agonist m-CPBG (40.0 nmol, i.c.v.) did not reveal considerable interstrain correlations between 5-HT(7) and 5-HT(1A) or 5-HT(3) receptor-induced hypothermia. The selective 5-HT(7) receptor antagonist SB 269970 (16.1 fmol, i.c.v.) failed to attenuate the hypothermic effect of 8-OH-DPAT 1.0 mg/kg, i.p. (3.0 μmol/kg) and m-CPBG (40.0 nmol, i.c.v.) indicating that the brain 5-HT(7) receptor is not involved in the hypothermic effects of 8-OH-DPAT or m-CPBG. The obtained results suggest that the central 5-HT(7) receptor plays an essential role in the mediation of thermoregulation independent of 5-HT(1A) and 5-HT(3) receptors.

• Authors: Vladimir S Naumenko, Elena M Kondaurova, Nina K Popova
• Journal: Neuropharmacology (Neuropharmacology) Vol. 61 Issue 8 Pg. 1360-5 (Dec 2011) ISSN: 1873-7064 [Electronic] England
• PMID: 21884711 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Receptors, Serotonin
• Receptors, Serotonin, 5-HT3
• Serotonin Agents
• serotonin 7 receptor
• Receptor, Serotonin, 5-HT1A
• Serotonin

Topics

• Analysis of Variance
• Animals
• Body Temperature (drug effects)
• Brain (metabolism)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Hypothermia (chemically induced, pathology)
• Male
• Mice
• Mice, Inbred Strains
• Receptor, Serotonin, 5-HT1A (metabolism)
• Receptors, Serotonin (metabolism)
• Receptors, Serotonin, 5-HT3 (metabolism)
• Serotonin (adverse effects)
• Serotonin Agents (pharmacology)
• Species Specificity