Genetic Dissection of the Tail Suspension Test: A Mouse Model of Stress Vulnerability and Antidepressant Response

• Published in: Biological psychiatry (1969) 2007-07, Vol.62 (1), p.81-91
• Main Authors: Liu, Xiaoqing, Stancliffe, Devin, Lee, Samuel, Mathur, Shelly, Gershenfeld, Howard K
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Animal model; Animals; antidepressant; Antidepressive Agents - pharmacology; Antidepressive Agents - therapeutic use; Behavior, Animal - drug effects; Behavior, Animal - physiology; behavioral despair; Biological and medical sciences; Chromosome Mapping; Chromosomes, Mammalian - genetics; Crosses, Genetic; Depression; Disease Models, Animal; Fever - genetics; Genetic Predisposition to Disease - genetics; Hindlimb Suspension - physiology; hyperthermia; imipramine; Imipramine - pharmacology; Imipramine - therapeutic use; Immobilization - physiology; Immobilization - psychology; Immunohistochemistry; Injections, Intraperitoneal; linkage; Lod Score; Medical sciences; Mice; Mice, Inbred Strains; Mood disorders; Neuropharmacology; Pharmacology. Drug treatments; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Quantitative Trait Loci - genetics; Receptors, Cell Surface - genetics; Receptors, GABA-A - drug effects; Receptors, GABA-A - genetics; Receptors, Leptin; stress vulnerability; Stress, Psychological - drug therapy; Stress, Psychological - etiology; Stress, Psychological - genetics; Terminology as Topic
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2006.08.017

Background The tail suspension test (TST) is a mouse screening test for antidepressants. Methods An F2 intercross was derived from NMRI and 129S6 inbred strains (n = 747). Mice underwent standardized TST with 2 sessions: (1) baseline and (2) imipramine (30 mg/kg, intraperitoneally) TST. Results A whole genome scan of this intercross mapped significant basal TST quantitative trait loci (QTL) on chromosomes (chr) 5 (peak 61 cM, Lod 5.7), 12 (peak 43 cM, Lod 5.2), and 18 (peak 51 cM, Lod 3.0). A suggestive QTL on chr 4 (peak 62 cM; Lod 3.1) overlapped regions containing previously mapped QTLs. For TST imipramine response, QTL were mapped on chr 1, 4, and 5. The chromosome 5 locus affected basal TST, antidepressant immobility response, and tail suspension-induced hyperthermia (TSIH) behaviors. An outbred NMRI F2 population provided further evidence for a chr 5 QTL. This chr 5 region harbors a cluster of gamma aminobutyric acid (GABA)-A receptor subunits and the human syntenic region includes chr 4p, 1p11, 12q24, and 22q11.24. A significant TSIH QTL (Tsih1) mapped on chr 4 near the Leptin receptor (Lepr). Conclusions These QTL provide potential regions of interest for human genetic studies in stress-diathesis models of psychiatric illness and antidepressant responsiveness.