Immobility responses between mouse strains correlate with distinct hippocampal serotonin transporter protein expression and function.
Mouse strain differences in immobility and in sensitivity to antidepressants have been observed in the forced swimming test (FST) and the tail suspension test (TST). However, the neurotransmitter systems and neural substrates that contribute to these differences remain unknown. To investigate the role of the hippocampal serotonin transporter (5-HTT), we measured baseline immobility and the immobility responses to fluoxetine (FLX) in the FST and the TST in male CD-1, C57BL/6, DBA and BALB/c mice. We observed strain differences in baseline immobility time, with CD-1 mice showing the longest and DBA mice showing the shortest. In contrast, DBA and BALB/c mice showed the highest sensitivity to FLX, whereas CD-1 and C57BL/6 mice showed the lowest sensitivity. Also we found strain differences in both the total 5-HTT protein level and the membrane-bound 5-HTT level (estimated by V max) as follows: DBA>BALB/c>CD-1=C57BL/6. The uptake efficiency of the membrane-bound 5-HTT (estimated by 1/K m) was highest in DBA and BALB/c mice and lowest in CD-1 and C57BL/6 mice. A correlation analysis of subregions within the hippocampus revealed that immobility time was negatively correlated with V max and positively correlated with K m in the hippocampus. Therefore a higher uptake capacity of the membrane-bound 5-HTT in the hippocampus was associated with lower baseline immobility and greater sensitivity to FLX. These results suggest that alterations in hippocampal 5-HTT activity may contribute to mouse strain differences in the FST and the TST.
Department of Clinical Pharmacology, School of Pharmacy,China Medical University,Shenyang, 110001,China.
Man
M
Tang
Department of Clinical Pharmacology, School of Pharmacy,China Medical University,Shenyang, 110001,China.
Tao
T
He
Department of Burns,The Northern Hospital,Shenyang, 110016,China.
Qing-yan
QY
Meng
Department of Neuroscience,Baylor College of Medicine,Houston, TX 77030,USA.
John Isaac
JI
Broussard
Department of Scientific Research,Shenyang Hospital of Traditional Chinese Medicine,Shenyang, 110004,China.
Lan
L
Yao
Center of Experiment and Technology,China Medical University,Shenyang, 110001,China.
Yao
Y
Diao
Department of Seven-year Clinical Medicine,China Medical University,Shenyang, 110004,China.
Xiu-bo
XB
Sang
Department of Seven-year Clinical Medicine,China Medical University,Shenyang, 110004,China.
Qing-peng
QP
Liu
Department of Physiology, College of Basic Medicine,China Medical University,Shenyang, 110001,China.
Ying-jun
YJ
Liao
Department of Ultrasonography,The First Affiliated Hospital of China Medical University,110001,China.
Yuge
Y
Li
Department of Integrative Biology,University of Texas,Austin, 78712,USA.
Shulei
S
Zhao
D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology; D019417:Hindlimb Suspension; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D046353:Immobility Response, Tonic / Q000187:drug effects / Q000502:physiology*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D011877:Radionuclide Imaging; D012701:Serotonin / Q000378:metabolism / Q000493:pharmacokinetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013045:Species Specificity; D013223:Statistics as Topic; D013550:Swimming / Q000523:psychology; D013574:Synaptosomes / Q000000981:diagnostic imaging / Q000187:drug effects; D014316:Tritium / Q000493:pharmacokinetics
D005473:Fluoxetine; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D014316:Tritium; C493231:Slc6a4 protein, mouse