Hypolocomotion, anxiety and serotonin syndrome-like behavior contribute to the complex phenotype of serotonin transporter knockout mice

Genes, Brain and Behavior

Volumn 6, Issue 4, 2007, Pages 389-400

  Kalueff, A V ^a   Fox, M A ^a   Gallagher, P S ^a   Murphy, D L ^a  

^a NATIONAL INSTITUTE OF MENTAL HEALTH   (United States)

Author keywords

Activity; Anxiety; Behavioral phenotype; Knockout mice; Serotonin syndrome like behavior; Serotonin transporter

Indexed keywords

SEROTONIN; SEROTONIN TRANSPORTER;

ANIMAL BEHAVIOR; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANXIETY; ARTICLE; COGNITION; CONTROLLED STUDY; EXPLORATORY BEHAVIOR; FEMALE; GAIT DISORDER; GROOMING; HYPOLOCOMOTION; KNOCKOUT MOUSE; MOTOR COORDINATION; MOTOR DYSFUNCTION; MOUSE; NESTING; NONHUMAN; OPEN FIELD TEST; PRIORITY JOURNAL; SENSORY NERVE; SEROTONIN LIKE SYNDROME; SEROTONIN SYNDROME; SOCIAL INTERACTION; TIC; TREMOR; WILD TYPE;

ANIMALS; ANXIETY; EXPLORATORY BEHAVIOR; FEMALE; GENETICS, BEHAVIORAL; HYPOKINESIA; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MOTOR ACTIVITY; SENSATION; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; SEROTONIN SYNDROME; SOCIAL BEHAVIOR; STATISTICS, NONPARAMETRIC; STEREOTYPED BEHAVIOR;

MUS;

EID: 34249065202     PISSN: 16011848     EISSN: 1601183X     Source Type: Journal    
DOI: 10.1111/j.1601-183X.2006.00270.x     Document Type: Article

References (85)

1. Bacchelli, E. Maestrini, E 2006) Autism spectrum disorders: molecular genetic advances. Am J Med Genet C Semin Med Genet 142, 13 23.
2. Bengel, D., Murphy, D.L., Andrews, A.M., Wichems, C.H., Feltner, D., Heils, A., Mossner, R., Westphal, H Lesch, K.P 1998) Altered brain serotonin homeostasis and locomotor insensitivity to 3, 4-methylenedioxymethamphetamine ("Ecstasy") in serotonin transporter-deficient mice. Mol Pharmacol 53, 649 655.
3. Blakely, R.D 2001) Physiological genomics of antidepressant targets: keeping the periphery in mind. J Neurosci 21, 8319 8323.
4. Borsini, F., Brambilla, A., Cesana, R. Grippa, N 2001) Lack of interaction between flibanserin and antidepressants in inducing serotonergic syndrome in rats. Int J Neuropsychopharmacol 4, 9 15.
5. Bouali, S., Evrard A., Chastanet M., Lesch K.P., Hamon M. Adrien J 2003) Sex hormone-dependent desensitization of 5-HT1A autoreceptors in knockout mice deficient in the 5-HT transporter. Eur J Neurosci 18, 2203 2212.
6. Boyer, E.W. Shannon, M 2005) The serotonin syndrome. New Engl J Med 352, 1112 1120.
7. Bulloch, K., Hamburger, R.N. Loy, R 1982) Nest-building behavior in two cerebellar mutant mice: staggerer and weaver. Behav Neural Biol 36, 94 97.
8. Chou-Green, J.M., Holscher, T.D., Dallman, M.F. Akana, S.F 2003) Compulsive behavior in the 5-HT2C receptor knockout mouse. Physiol Behav 78, 641 649.
9. Conroy, J., Meally, E., Kearney, G., Fitzgerald, M., Gill, M. Gallagher, L 2004) Serotonin transporter gene and autism: a haplotype analysis in an Irish autistic population. Mol Psychiatry 9, 587 593.
10. Cornelissen, L.L., Brooks, D.P. Wibberley, A 2005) Female, but not male, serotonin reuptake transporter (5-HTT) knockout mice exhibit bladder instability. Auton Neurosci 122, 107 110.
11. Crawley, J.N 2000) What's Wrong with My Mouse? Behavioral Phenotyping of Transgenic and Knockout Mice. Wiley-Liss, New York.
12. Crawley, J.N 2004) Designing mouse behavioral tasks relevant to autistic-like behaviors. Ment Retard Dev Disabil Res Rev 10, 248 258.
13. Crawley, J.N. Paylor, R 1997) A proposed test battery and constellations of specific behavioral paradigms to investigate the behavioral phenotypes of transgenic and knockout mice. Horm Behav 31, 197 211.
14. Darmani, N.A. Ahmad, B 1999) Long-term sequential determination of behavioral ontogeny of 5-HT1a and 5-HT2 receptor functions in the rat. J Pharmacol Exper Ther 288, 247 253.
15. Esaki, T., Cook, M., Shimoji, K., Murphy, D.L., Sokoloff, L. Holmes, A 2005) Developmental disruption of serotonin transporter function impairs cerebral responses to whisker stimulation in mice. Proc Natl Acad Sci USA 102, 5582 5587.
16. Ferrari, P.F., Palanza, P., Parmigiani, S. Rodgers, R.J 1998) Interindividual variability in Swiss male mice: relationship between social factors, aggression, and anxiety. Physiol Behav 63, 821 827.
17. File, S.E 1980) The use of social interaction as a method for detecting anxiolytic activity of chlordiazepoxide-like drugs. J Neurosci Methods 2, 219 238.
18. File, S.E. Seth, P 2003) A review of 25 years of the social interaction test. Eur J Pharmacol 463, 35 53.
19. Fox, M.A. Murphy, D.L 2006) Exaggerated serotonin syndrome in serotonin transporter knockout mice. Int J Neuropsychopharmacology 9, S174.
20. Geyer, M.A. Markou A 2002) The role of preclinical models in the development of psychotropic drugs. In Davis, K.L., Charney, D. Coyle, J.T. (eds Neuropsychopharmacology: The Fifth Generation of Progress. Lippincott Williams and Wilkins, New York, pp. 445 455.
21. Gillman, P.K 2006) A review of serotonin toxicity data: implications for the mechanisms of antidepressant drug action. Biol Psychiatry 59, 1046 1051.
22. Gingrich, J.A. Hen, R 2001) Dissecting the role of the serotonin system in neuropsychiatric disorders using knockout mice. Psychopharmacology 155, 1 10.
23. Goitz, F 2002) Serotonin syndrome. Utox Update 4, 1 4.
24. Holmes, A., Yang, R.J., Murphy, D.L. Crawley, J.N 2002a) Evaluation of antidepressant-related behavioral responses in mice lacking the serotonin transporter. Neuropsychopharmacology 27, 914 923.
25. Holmes, A., Murphy, D.L. Crawley, J.N 2002b) Reduced aggression in mice lacking the serotonin transporter. Psychopharmacology 161, 160 167.
26. Holmes, A., Lit, Q., Murphy, D.L., Gold, E. Crawley, J.N 2003a) Abnormal anxiety-related behavior in serotonin transporter null mutant mice: the influence of genetic background. Genes Brain Behav 2, 365 380.
27. Holmes, A., Yang, R.J., Lesch, K.P., Crawley, J.N. Murphy, D.L 2003b) Mice lacking the serotonin transporter exhibit 5-HT(1A) receptor-mediated abnormalities in tests for anxiety-like behavior. Neuropsychopharmacology 28, 2077 2088.
28. Holmes, A., Murphy, D.L. Crawley, J.N 2003c) Abnormal behavioral phenotypes of serotonin transporter knockout mice: parallels with human anxiety and depression. Biol Psychiatry 54, 953 959.
29. Hossain, S.M., Wong, B.K. Simpson, E.M 2004) The dark phase improves genetic discrimination for some high throughput mouse behavioral phenotyping. Genes Brain Behav 3, 167 177.
30. Hunter, A.J., Hatcher, J., Virley, D., Nelson, P., Irving, E., Hadingham, S.J Parsons, A.A 2000) Functional assessments in mice and rats after focal stroke. Neuropharmacology 39, 806 816.
31. Insel, T., Roy, B., Cohen, R.M. Murphy, D.L 1982) Possible development of the serotonin syndrome in man. Am J Psychiatry 7, 954 955.
32. Isbister, G.K. Buckley, N.A 2005) The pathophysiology of serotonin toxicity in animals and humans. Clin Neuropharmacol 28, 205 214.
33. Izidio, G.S., Lopes, D.M., Spricigo, L. Ramos, A 2005) Common variations in the pretest environment influence genotypic comparisons in models of anxiety. Genes Brain Behav 4, 412 419.
34. Izumi, T., Iwamoto, N., Kitaichi, Y., Kato, A., Inoue, T. Koyama, T in press) Effects of co-administration of a selective serotonin reuptake inhibitor and monoamine oxidase inhibitors on 5-HT-related behavior in rats. Eur J Pharmacol.
35. Kalueff, A.V. Tuohimaa, P 2004) Grooming analysis algorithm for neurobehavioural stress research. Brain Res Protoc 13, 151 158.
36. Kalueff, A.V. Tuohimaa, P 2005) The Suok ("ropewalking") murine test of anxiety. Brain Res Brain Res Protoc 14, 87 99.
37. Kalueff, A.V., Keisala, T., Minasyan, A., Kuuslahti, M., Miettinen, S. Tuohimaa, P 2006) Behavioural anomalies in mice evoked by "Tokyo" disruption of the Vitamin D receptor gene. Neurosci Res 54, 254 260.
38. Kalueff, A.V., Gallagher, P.S. Murphy, D.L in press) Are the serotonin transporter knockout mice "depressed"?: hypoactivity but no anhedonia. Neuroreport.
39. Katz, R.J 1979) Stress induced Straub tail elevation. Further behavioral evidence in rats for the involvement of endorphins in stress. Neurosci Lett 13, 249 252.
40. Kim, D.K., Tolliver, T.J., Huang, S.J., Martin, B.J., Andrews, A.M., Wichems, C., Holmes, A., Lesch, K.P Murphy D.L 2005) Altered serotonin synthesis, turnover and dynamic regulation in multiple brain regions of mice lacking the serotonin transporter. Neuropharmacology 49, 798 810.
41. Lanfumey, L., Mannoury La Cour, C., Froger, N. Hamon, M 2000) 5-HT-HPA interactions in two models of transgenic mice relevant to major depression. Neurochem Res 25, 1199 1206.
42. Lathe, R 2004) The individuality of mice. Genes Brain Behav 3, 317 327.
43. Lesch, K.P., Bengel, D., Heils, A., Sabol, S.Z., Greenberg, B.D., Petri, S., Benjamin, J., Muller, C.R., Hamer, D.H Murphy, D.L 1996) Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274, 1527 1531.
44. Lesch, K.P 2002) Neuroticism and serotonin: a developmental genetic perspective. In Plomin, R., DeFries, J.C., Craig, J.W. McGuffin, P. (eds Behavioral Genetics in the Postgenomic Era. APA, New York, pp. 389 423.
45. Lesch, K.P., Zeng, Y., Reif, A. Gutknecht, L 2003) Anxiety-related traits in mice with modified genes of the serotonergic pathway. Eur J Pharmacol 480, 185 204.
46. Li, Q., Wichems, C., Heils, A., Van De Kar, L.D., Lesch, K.P. Murphy, D.L 1999) Reduction of 5-hydroxytryptamine (5-HT)(1A)-mediated temperature and neuroendocrine responses and 5-HT(1A) binding sites in 5-HT transporter knockout mice. J Pharmacol Exp Ther 291, 999 1007.
47. Li, Q., Wichems, C., Heils, A., Lesch, K.P. Murphy, D.L 2000) Reduction in the density and expression, but not G-protein coupling, of serotonin receptors (5-HT1A) in 5-HT transporter knock-out mice: gender and brain region differences. J Neurosci 20, 7888 7895.
48. Li, Q., Wichems, C.H., Ma, L., Van de Kar, L.D., Garcia, F. Murphy, D.L 2003) Brain region-specific alterations of 5-HT2A and 5-HT2C receptors in serotonin transporter knockout mice. J Neurochem 84, 1256 1265.
49. Lira, A., Zhou, M., Castanon, N., Ansorge, M.S., Gordon, J.A., Francis, J.H., Bradley-Moore, M., Lira, J., Underwood, M.D., Arango, V., Kung, H.F., Hofer, M.A., Hen, R Gringrich, J.A 2003) Altered depression-related behaviors and functional changes in the dorsal raphe nucleus of serotonin transporter-deficient mice. Biol Psychiatry 54, 960 971.
50. Mannoury la Cour, C., Hanoun, N., Melfort, M., Hen, R., Lesch, K.P., Hamon, M. Lanfumey, L 2004) GABA(B) receptors in 5-HT transporter- and 5-HT1A receptor-knock-out mice: further evidence of a transduction pathway shared with 5-HT1A receptors. J Neurochem 89, 886 896.
51. Mathews, T.A., Fedele, D.E., Coppelli, F.M., Avila, A.M., Murphy, D.L. Andrews, A.M 2004) Gene dose-dependent alterations in extraneuronal serotonin but not dopamine in mice with reduced serotonin transporter expression. J Neurosci Methods 140, 169 181.
52. McCauley, J.L., Olson, L.M., Dowd, M., Amin, T., Steele, A., Blakely, R.D., Folstein, S.E., Haines, J.L Sutcliffe, J.S 2004) Linkage and association analysis at the serotonin transporter (SLC6A4) locus in a rigid-compulsive subset of autism. Am J Med Genet 127, 104 112.
53. McIlwain, K.L., Merriweather, M.Y., Yuva-Paylor, L.A. Paylor, R 2001) The use of behavioral test batteries: effects of training history. Physiol Behav 73, 705 717.
54. Montanez, S., Owens, W.A., Gould, G.G., Murphy, D.L. Daws, L.C 2003) Exaggerated effect of fluvoxamine in heterozygote serotonin transporter knockout mice. J Neurochem 86, 210 219.
55. Moretti, P., Bouwknecht, J.A., Teague, R., Paylor, R. Zoghbi, H.Y 2005) Abnormalities of social interactions and home-cage behavior in a mouse model of Rett syndrome. Hum Mol Genet 14, 205 220.
56. Mossner, R., Albert, D., Persico, A.M., Hennig, T., Bengel, D., Holtmann, B., Schmitt, A., Keller, F., Simantov, R., Murphy, D., Seif, I., Deckert, J Lesch, K.P 2000) Differential regulation of adenosine A(1) and A(2A) receptors in serotonin transporter and monoamine oxidase A-deficient mice. Eur Neuropsychopharmacol 10, 489 493.
57. Moy, S.S., Nadler, J.J., Perez, A., Barbaro, R.P., Johns, J.M., Magnuson, T.R., Piven, J Crawley, J.N 2004) Sociability and preference for social novelty in five inbred strains: an approach to assess autistic-like behavior in mice. Genes Brain Behav 3, 287 302.
58. Moy, S.S., Nadler, J.J., Magnuson, T.R. Crawley, J.N 2006) Mouse models of autism spectrum disorders: the challenge for behavioral genetics. Am J Med Genet C Semin Med Genet 142, 40 51.
59. Murphy, D.L., Li, Q., Engel, S., Wichems, C., Andrews, A., Lesch, K.P. Uhl, G 2001) Genetic perspectives on the serotonin transporter. Brain Res Bull 56, 487 494.
60. Murphy, D.L., Uhl, G.R., Holmes, A., Ren-Patterson, R., Hall, F.S., Sora, I., Detena-Wadleigh, S Lesch, K.P 2003) Experimental gene interaction studies with SERT mutant mice as models for human polygenic and epistatic traits and disorders. Genes Brain Behav 2, 350 364.
61. Murphy, D.L., Lerner, A., Rudnick, G. Lesch, K.P 2004) Serotonin transporter: gene, genetic disorders, and pharmacogenetics. Mol Interv 4, 109 123.
62. Nisijima, K., Yoshino, T. Ishiguro, T 2000) Risperidone counteracts lethality in an animal model of the serotonin syndrome. Psychopharmacology 150, 9 14.
63. Nordstrom, E.J. Burton, F.H 2002) A transgenic model of comorbid Tourette's syndrome and obsessive-compulsive circuitry. Mol Psychiatry 7, 617 625.
64. Paylor R., Spencer, C.M., Yuva-Paylor, L.A. Pieke-Dahl, S 2006) The use of behavioral test batteries, II: effect of test interval. Physiol Behav 87, 95 102.
65. Persico, A.M., Mengual, E., Moessner, R., Hall, F.S., Revay, R.S., Sora, I, Arellano, J., DeFelipe, J., Gimenez-Amaya, J.M., Conciatori, M., Marino, R., Baldi, A., Cabib, S., Pascucci, T., Unl, G.R., Murphy, D.L., Lesch, K.P Keller, F 2001) Barrel pattern formation requires serotonin uptake by thalamocortical afferents, and not vesicular monoamine release. J Neurosci 21, 6862 6873.
66. Pinto, L.H. Enroth-Cugell, C 2000) Tests of the mouse visual system. Mamm Genome 11, 531 536.
67. Qu, Y., Villacreses, N., Murphy, D.L. Rapoport, S.I 2005) 5-HT2A/2C receptor signaling via phospholipase A2 and arachidonic acid is attenuated in mice lacking the serotonin reuptake transporter. Psychopharmacology 180, 12 20.
68. Ravary, A., Muzerelle, A., Darmon, M., Murphy, D.L., Moessner, R., Lesch, K.P. Gaspar, P 2001) Abnormal trafficking and subcellular localization of an N-terminally truncated serotonin transporter protein. Eur J Neurosci 13, 1349 1362.
69. Salichon, N., Gaspar, P., Upton, A.L., Picaud, S., Hanoun, N., Hamon., M, De Maeyer, E., Murphy, D.L., Mossner, R., Lesch, K.P, Hen, R Seif, I 2001) Excessive activation of serotonin (5-HT) 1B receptors disrupts the formation of sensory maps in monoamine oxidase A and 5-ht transporter knock-out mice. J Neurosci 21, 884 896.
70. Schmitt, A., Mossner, R., Gossmann, A., Fischer, I.G., Gorboulev, V., Murphy, D.L., Koepsell, H Lesch, K.P 2003) Organic cation transporter capable of transporting serotonin is up-regulated in serotonin transporter-deficient mice. J Neurosci Res 71, 701 719.
71. Shioda, K., Nisijima, K., Yoshino, T. Kato, S 2004) Extracellular serotonin, dopamine and glutamate levels are elevated in the hypothalamus in a serotonin syndrome animal model induced by tranylcypromine and fluoxetine. Progr Neuropsychopharmacol Biol Psychiatry 28, 633 640.
72. Sousa, N., Almeida, O.F. Wotjak, C.T 2006) A hitchhiker's guide to behavioral analysis in laboratory rodents. Genes Brain Behav 5 Suppl 2, 5 24.
73. Sutcliffe, J.S., Delahanty, R.J., Prasad, H.C., McCauley, J.L., Han, Q., Jiang, L., Li, C., Folstein, S.E Blakely, R.D 2005) Allelic heterogeneity at the serotonin transporter locus (SLC6A4) confers susceptibility to autism and rigid-compulsive behaviors. Am J Hum Genet 77, 265 279.
74. Thompson, A.M. Lauder, J.M 2005) Postnatal expression of the serotonin transporter in auditory brainstem neurons. Dev Neurosci 27, 1 12.
75. Torres, G.E., Gainetdinov, R.R. Caron, M.G 2003) Plasma membrane monoamine transporters: structure, regulation and function. Nat Rev Neurosci 4, 13 25.
76. Van der Staay, F.J. Steckler, T 2002) The fallacy of behavioral phenotyping without standardisation. Genes Brain Behav 1, 9 13.
77. Vogel, C., Mossner, R., Gerlach, M., Heinemann, T., Murphy, D.L., Riederer, P., Lesch, K.P Sommer, C 2003) Absence of thermal hyperalgesia in serotonin transporter-deficient mice. J Neurosci 23, 708 715.
78. Wendland. J.R., Martin, B.J., Kruse, M.R., Lesch, K.P. Murphy, D.L 2006) Simultaneous genotyping of four functional loci of human SLC6A4, with a reappraisal of 5-HTTLPR and rs25531. Mol Psychiatry 11, 224 226.
79. Wisor, J.P., Wurts, S.W., Hall, F.S., Lesch, K.P., Murphy, D.L., Uhl, G.R. Edgar, D.M 2003) Altered rapid eye movement sleep timing in serotonin transporter knockout mice. Neuroreport 14, 233 238.
80. Wong, M.L. Licinio, J 2004) From monoamines to genomic targets: a paradigm shift for drug discovery in depression. Nat Rev Drug Discov 3, 136 151.
81. Xu, Y., Sari, Y. Zhou, F.C 2004) Selective serotonin reuptake inhibitor disrupts organization of thalamocortical somatosensory barrels during development. Dev Brain Res 150, 151 161.
82. Yonan, A.L., Alarcon, M., Cheng, R., Magnusson, P.K., Spence, S.J., Palmer, A.A., Grum, A., Juo, S.H., Terwilliger, J.D., Liu, J., Cantor, R.M., Geschwind, D.H Gilliam, T.C 2003) A genomewide screen of 345 families for autism-susceptibility loci. Am J Hum Genet 73, 886 897.
83. Zhao, S., Edwards, J., Carroll, J., Wiedholz, L., Millstein, R.A., Jaing, C., Murphy, D.L., Lanthorn, T.H Holmes, A 2006) Insertion mutation at the C-terminus of the serotonin transporter disrupts brain serotonin function and emotion-related behaviors in mice. Neuroscience 140, 321 334.
84. Zhou, F.C., Lesch, K.P. Murphy, D.L 2002) Serotonin uptake into dopamine neurons via dopamine transporters: a compensatory alternative. Brain Res 942, 109 119.
85. Zhuang, X., Masson, J., Gingrich, J.A., Rayport, S., Hen, R 2005) Targeted gene expression in dopamine and serotonin neurons of the mouse brain. J Neurosci Methods 143, 27 32.