Hypothermic responses to 8-OH-DPAT in the Ts65Dn mouse model of Down syndrome.
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.
Stasko
Melissa R
MR
Eleanor Roosevelt Institute, University of Denver, Denver, Colorado 80206, USA.
Scott-McKean
Jonah J
JJ
Costa
Alberto C S
AC
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics*; D007035:Hypothermia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C104425:serotonin 7 receptor; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin