Department of Behavioral Neurogenomics, Institute of Cytology and Genetics, Siberian Division of Russian Academy of Science, Novosibirsk, Russia.
Neuropharmacology. 2011 Dec;61(8):1360-5. doi: 10.1016/j.neuropharm.2011.08.022. Epub 2011 Aug 23.
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.
脑室给予选择性 5-羟色胺 5-HT(7)受体激动剂 LP44（4-[2-（甲硫基）苯基]-N-[1,2,3,4-四氢-1-萘基]-1-哌啶基]-1-戊酰胺盐酸盐；10.3、20.5 或 41.0 nmol）可使 CBA/Lac 小鼠产生明显的体温过低反应。LP44 诱导的（20.5 nmol）体温过低反应被选择性 5-HT(7)受体拮抗剂 SB 269970（16.1 fmol，脑室）预处理显著减弱。同时，腹腔内给予 LP44 在广泛的剂量范围内 1.0、2.0 或 10.0 mg/kg（2.0、4.0、20.0 μmol/kg）不会引起明显的体温过低反应。这些发现表明，中枢而不是外周 5-HT(7)受体参与了体温过低的调节。比较了 LP44 诱导的（20.5 nmol）在八种近交系小鼠（DBA/2J、CBA/Lac、C57BL/6、BALB/c、ICR、AKR/J、C3H 和 Asn）中的体温过低反应，发现基因型有显著影响。在相同的八种小鼠品系中，研究了 5-HT(1A)和 5-HT(3)受体的功能活性。比较了 5-HT(7)受体激动剂 LP44（20.5 nmol，脑室）和 5-HT(1A)受体激动剂 8-OH-DPAT 1.0 mg/kg，腹腔内注射（3.0 μmol/kg），5-HT(3)受体激动剂 m-CPBG（40.0 nmol，脑室）引起的体温过低反应，发现 5-HT(7)和 5-HT(1A)或 5-HT(3)受体诱导的体温过低之间没有相当大的种间相关性。选择性 5-HT(7)受体拮抗剂 SB 269970（16.1 fmol，脑室）未能减弱 8-OH-DPAT 1.0 mg/kg，腹腔内注射（3.0 μmol/kg）和 m-CPBG（40.0 nmol，脑室）的体温过低作用，表明脑 5-HT(7)受体不参与 8-OH-DPAT 或 m-CPBG 的体温过低作用。这些结果表明，中枢 5-HT(7)受体在独立于 5-HT(1A)和 5-HT(3)受体的体温调节中介导中起重要作用。
