Hypothermic responses to 8-OH-DPAT in the Ts65Dn mouse model of Down syndrome

Neuroreport. 2006 May 29;17(8):837-41. doi: 10.1097/01.wnr.0000220129.78726.bb.

Abstract

Recently, we have demonstrated that potassium channels containing G-protein-activated potassium channel 2 (GIRK2) subunits play a significant role in hypothermia induced by several neurotransmitter receptor agonists, including the serotonin (5-HT)1A/5-HT7 receptor agonist 8-OH-DPAT [R-(+)-8-hydroxy-2-(di-n-propylamino) tetralin]. The GIRK2 gene is located in human chromosome 21 (its mouse ortholog, Girk2, is in mouse chromosome 16). Down syndrome is produced by the trisomy of chromosome 21. Here, we used quantitative radiotelemetry to investigatehypothermic responses to 8-OH-DPAT in the Down syndrome mouse model Ts65Dn (which carries an extra chromosomal 16 segment containing Girk2). Our results indicate that, in relation to euploid controls, Ts65Dn mice display significantly increased hypothermic responses to 8-OH-DPAT. This finding may be relevant to the understanding of previously reported differences in serotoninergic neurotransmission in persons with Down syndrome.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology*
  • Animals
  • Brain / drug effects
  • Brain / physiopathology*
  • Disease Models, Animal
  • Down Syndrome / genetics
  • Down Syndrome / metabolism
  • Down Syndrome / physiopathology*
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / genetics*
  • Hypothermia / genetics
  • Hypothermia / metabolism
  • Hypothermia / physiopathology*
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Neurologic Mutants
  • Receptor, Serotonin, 5-HT1A / drug effects
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / metabolism*
  • Serotonin / metabolism
  • Serotonin Receptor Agonists / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / genetics

Substances

  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • Receptors, Serotonin
  • Serotonin Receptor Agonists
  • serotonin 7 receptor
  • Receptor, Serotonin, 5-HT1A
  • Serotonin
  • 8-Hydroxy-2-(di-n-propylamino)tetralin