Cellular and molecular alterations in mice with deficient and reduced serotonin transporters

Molecular Neurobiology

Volumn 34, Issue 1, 2006, Pages 51-65

  Li, Qian ^a  

^a University of Texas Medical Branch School of Medicine   (United States)

Author keywords

5 HT metabolism; 5 HT receptors; 5 HT1A receptors; Anxiety; Development; Dopamine transporter; HPA axis; Stress

Indexed keywords

SEROTONIN 1B RECEPTOR; SEROTONIN 2A RECEPTOR; SEROTONIN 2C RECEPTOR; SEROTONIN RECEPTOR; SEROTONIN TRANSPORTER;

AGGRESSION; BEHAVIOR; CELL ACTIVITY; HUMAN; HYPOTHALAMUS HYPOPHYSIS SYSTEM; MEMBRANE TRANSPORT; MOLECULAR DYNAMICS; MOOD; MOOD DISORDER; MUTATION; NEUROTRANSMISSION; NONHUMAN; PERSONALITY; PHENOTYPE; RECEPTOR BINDING; REVIEW;

EID: 33749055310     PISSN: 08937648     EISSN: None     Source Type: Journal    
DOI: 10.1385/MN:34:1:51     Document Type: Review

References (89)

1. Zhou F. C., Tao-Cheng J. H., Segu L., Patel T., and Wang Y. (1998) Serotonin transporters are located on the axons beyond the synaptic junctions: anatomical and functional evidence. Brain Res. 805, 241-254.
2. Owens M. J. (1997) Molecular and cellular mechanisms of antidepressant drugs. Depress. Anx. 1996-97. 4, 153-159.
3. Artigas F., Bel N., Casanovas J. M., and Romero L. (1996) Adaptative changes of the serotonergic system after antidepressant treatments. Adv. Exp. Med. Biol. 398, 51-59.
4. Caspi A., Sugden K., Moffitt T. E., et al. (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301, 386-389.
5. Lesch K. P., Bengel D., Heils A., et al. (1996) Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274, 1527-1531.
6. Lesch K. P. and Mossner R. (1998) Genetically driven variation in serotonin uptake: is there a link to affective spectrum, neurodevelopmental, and neurodegenerative disorders? Biol. Psychiatr. 44, 179-192.
7. Murphy D. L., Li Q., Engel S., et al. (2001) Genetic perspectives on the serotonin transporter. Brain Res. Bull. 56, 487-494.
8. Retz W., Retz-Junginger P., Supprian T., Thome J., and Rosler M. (2004) Association of serotonin transporter promoter gene polymorphism with violence: relation with personality disorders, impulsivity, and childhood ADHD psychopathology. Behav. Sci. Law 22, 415-425.
9. Heils A., Teufel A., Petri S., et al. (1996) Allelic variation of human serotonin transporter gene expression. J. Neurochem. 66, 2621-2624.
10. Holmes A., Yang R. J., Murphy D. L., and Crawley J. N. (2001) Abnormal emotional behaviors and age-related obesity in 5-HT transporter deficient mice. Soc. Neurosci. Abstr. 27, 987.5.
11. Greenberg B. D., Li Q., Lucas F. R., et al. (2000) Association between the serotonin transporter promoter polymorphism and personality traits in a primarily female population sample. American J. Med. Genet. 96, 202-216.
12. Hariri A. R., Mattay V. S., Tessitore A., et al. (2002) Serotonin transporter genetic variation and the response of the human amygdala. Science 297, 400-403.
13. Barr C. S., Newman T. K., Shannon C., et al. (2004) Rearing condition and Rh5-HTTLPR interact to influence limbic-hypothalamic-pituitary-adrenal axis response to stress in infant macaques. Biologic. Psychiatr. 55, 733-738.
14. Bengel D., Murphy D. L., Andrews A. M., et al. (1998) Altered brain serotonin homeostasis and locomotor insensitivity to 3,4-methylenedioxy- methamphetamine ("ecstasy") in serotonin transporter-deficient mice. Molecular Pharmacol. 53, 649-655.
15. Lira A., Zhou M. M., Castanon N., et al. (2003) Altered depression-related behaviors and functional changes in the dorsal raphe nucleus of serotonin transporter-deficient mice. Biol. Psychiatr. 54, 960-971.
16. Ansorge M. S., Zhou M. M., Lira A., Hen R., and Gingrich J. A. (2004) Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice. Science 306, 879-881.
17. Holmes A., Murphy D. L., and Crawley J. N. (2002) Reduced aggression in mice lacking the serotonin transporter. Psychopharmacology 161, 160-167.
18. Holmes A., Yang R. J., Lesch K. P., Crawley J. N., and Murphy D. L. (2003) Mice lacking the serotonin transporter exhibit 5-HT1A receptor-mediated abnormalities in tests for anxiety-like behavior. Neuropsychopharmacology 28, 2077-2088.
19. Holmes A., Murphy D. L., and Crawley J. N. (2003b) Abnormal behavioral phenotypes of serotonin transporter knockout mice: parallels with human anxiety and depression. Biol. Psychiatr. 54, 953-959.
20. Murphy D. L., Wichems C., Li Q., and Heils A. (1999) Molecular manipulations as tools for enhancing our understanding of 5-HT neurotransmission. Trends Pharmacol. Sci. 20, 246-252.
21. Murphy D. L., Lerner A., Rudnick G., and Lesch K. P. (2004) Serotonin transporter: gene, genetic disorders, and pharmacogenetics. Mol. Inter. 4, 109-123.
22. Perez X. A. and Andrews A. M. (2005) Chronoamperometry to determine differential reductions in uptake in brain synaptosomes from serotonin transporter knockout mice. Analyt. Chem. 77, 818-826.
23. Montanez S., Owens W. A., Gould G. G., Murphy D. L., and Daws L. C. (2003) Exaggerated effect of fluvoxamine in heterozygote serotonin transporter knockout mice. J. Neurochem. 86, 210-219.
24. Fabre V., Beaufour C., Evrard A., et al. (2000) Altered expression and functions of serotonin 5-HT1A and 5-HT1B receptors in knock-out mice lacking the 5-HT transporter. Eur. J. Neurosci. 12, 2299-2310.
25. Mathews T. A., Fedele D. E., Coppelli F. M., Avila A. M., Murphy D. L., and 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.
26. Kim D. K., Tolliver T. J., Huang S. J., et al. (2005) Altered serotonin synthesis, turnover and dynamic regulation in multiple brain regions of mice lacking the serotonin transporter. Neuropharmacology 49, 798-810.
27. Hoyer D., Clarke D. E., Fozard J. R., et al. (1994) VII. International union of pharmacology classification of receptors for 5-hydroxytryptamine (serotonin). Pharmacol. Rev. 46, 157-204.
28. Hoyer D., Hannon J. P., and Martin G. R. (2002) Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol. Biochem. Behav. 71, 533-554.
29. den Boer J. A., Bosker F. J., and Slaap B. R. (2000) Serotonergic drugs in the treatment of depressive and anxiety disorders. Human Psychopharmacol. Clin. Experiment.15, 315-336.
30. Graeff F. G., Guimaraes F. S., De Andrade T. G., and Deakin J. F. (1996) Role of 5-HT in Stress, Anxiety, and Depression. Pharmacol. Biochem. Behav. 54, 129-141.
31. Griebel G. (1995) 5-Hydroxytryptamine-interacting drugs in animal models of anxiety disorders: more than 30 years of research. Pharmacol. Ther. 65, 319-395.
32. Gingrich J. A. and Hen R. (2001) Dissecting the role of the serotonin system in neuropsychiatric disorders using knockout mice. Psychopharmacology 155, 1-10.
33. Groenink L., Pattij T., de Jongh R., et al. (2003) 5-HT1A receptor knockout mice and mice overexpressing corticotropin-releasing hormone in models of anxiety. Eur. J. Pharmacol. 463, 185-197.
34. Olivier B., Pattij T., Wood S. J., Oosting R., Sarnyai Z., and Toth M. (2001) The 5-HT1A receptor knockout mouse and anxiety. Behav. Pharmacol. 12, 439-450.
35. Holmes A., Li Q., Murphy D. L., Gold E., and Crawley J. N. (2003) Abnormal anxiety-related behaviour in serotonin transporter null mutant mice: the influence of genetic background. Genes Brain Behav. 2, 365-380.
36. Wichems C. H., Li Q., Holmes A., et al. (2000) Mechanisms mediating the increased anxiety-like behavior and excessive responses to stress in mice lacking the serotonin transporter. Soc. Neurosci. Abstr. 26, 400.
37. Li Q., Wichems C., Heils A., Lesch K. P., and 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.
38. Li Q., Wichems C., Heils A., Van de Kar L. D., Lesch K. P., and 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.
39. Gobbi G., Murphy D. L., Lesch K. P., and Blier P. (2001) Modifications of the serotonergic system in mice lacking serotonin transporters: an in vivo electrophysiological study. J. Pharmacol. Exp. Ther. 296, 987-995.
40. Lanfumey L., La Cour C. M., Froger N., and Hamon M. (2000) 5-HT-HPAinteractions in two models of transgenic mice relevant to major depression. Neurochem. Res. 25, 1199-1206.
41. Bouali S., Evrard A., Chastanet M., Lesch K. P., Hamon M., and Adrien J. (2003) Sex hormone-dependent desensitization of 5-HT1A autoreceptors in knockout mice deficient in the 5-HT transporter. Eur. J. Neuroscience 18, 2203-2212.
42. Bethea C. L., Gundlah C., and Mirkes S. J. (2000) Ovarian steroid action in the serotonin neural system of macaques. Novartis Found. Symp. 230, 112-130.
43. Carrasco G. A., Barker S. A., Zhang Y., et al. (2004) Estrogen treatment increases the levels of regulator of G protein signaling-Z1 in the hypothalamic paraventricular nucleus: possible role in desensitization of 5-hydroxytryptamine(1A) receptors. Neuroscience 127, 261-267.
44. D'Souza D. N., Zhang Y. H., Damjanoska K. J., et al. (2004) Estrogen reduces serotonin-1A receptor-mediated oxytocin release and G alpha(i/o/z) proteins in the hypothalamus of ovariectomized rats. Neuroendocrinology 80, 31-41.
45. Le Saux M. and Di Paolo T. (2005) Changes in 5-HT1A receptor binding and G-protein activation in the rat brain after estrogen treatment: comparison with tamoxifen and raloxifene. J. Psychiatr. Neurosci. 30, 110-117.
46. Lu N. Z. and Bethea C. L. (2002) Ovarian steroid regulation of 5-HT1A receptor binding and G protein activation in female monkeys. Neuropsychopharmacology 27, 12-24.
47. Azmitia E. C. (2001) Modern views on an ancient chemical: serotonin effects on cell proliferation, maturation, and apoptosis. Brain Res. Bull. 56, 413-424.
48. Azmitia E. C. and Whitaker-Azmitia P. M. (1997) Development and adult plasticity of serotoninergic neurons and their target cells, in Serotoninergic Neurons and 5-HT Receptors in the CNS, Baumgarten H. G. and Gothert M., eds, Berlin: Springer, pp. 1-39.
49. Whitaker-Azmitia P. M. (2005) Behavioral and cellular consequences of increasing serotonergic activity during brain development: a role in autism? Intern. J. Development. Neurosci. 23, 75-83.
50. Li Q., Holmes A., Ma L., Van de Kar L. D., Garcia F., and Murphy D. L. (2004) Medial hypothalamic 5-hydroxytryptamine (5-HT)1A receptors regulate neuroendocrine responses to stress and exploratory locomotor activity: application of recombinant adenovirus containing 5-HT1A sequences. J. Neurosci. 24, 10,868-10,877.
51. 1A agonist, in three stress paradigms: immobilization, forced swim and conditioned fear. Brain Res. 580, 205-214.
52. Saphier D., Farrar G. E., and Welch J. E. (1995) Differential inhibition of stress-induced adrenocortical responses by 5-HT1A agonists and by 5-HT2 and 5-HT3 antagonists. Psychoneuroendocrinology 20, 239-257.
53. Saphier D. and Welch J. E. (1995) Effects of the serotonin1A agonist, 8-hydroxy-2-(di-n- propylamino)tetralin on neurochemical responses to stress. J. Neurochem. 64, 767-776.
54. Li Q., Wichems C. H., Ma L., Van de Kar L. D., Garcia F., and 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.
55. Rioux A., Fabre V., Lesch K. P., et al. (1999) Adaptive changes of serotonin 5-HT2A receptors in mice lacking the serotonin transporter. Neurosci. Lett. 262, 113-116.
56. Hartig P. R., Hoffman B. J., Kaufman M. J., and Hirata F. (1990) The 5-HT1C receptor. Ann. NY Acad. Sci. 600, 149-166.
57. 2C receptors. Mol. Brain Res. 23, 163-178.
58. Broocks A., Bandelow B., George A., et al. (2000) Increased psychological responses and divergent neuroendocrine responses to M-CPP and ipsapirone in patients with panic disorder. Intern. Clin. Psychopharmacol. 15, 153-161.
59. Preuss U. W., Soyka M., Bahlmann M., et al. (2000) Serotonin transporter gene regulatory region polymorphism (5- HTTLPR), [H-3]paroxetine binding in healthy control subjects and alcohol-dependent patients and their relationships to impulsivity. Psych. Res. 96, 51-61.
60. Burns C. M., Chu H., Rueter S. M., et al. (1997) Regulation of serotonin-2C receptor G-protein coupling by RNA editing. Nature 387, 303-308.
61. Canton H., Emeson R. B., Barker E. L., et al. (1996) Identification, molecular cloning, and distribution of a short variant of the 5-Hydroxytryptamine2C receptor produced by alternative splicing. Mol Pharmacol 50, 799-807.
62. Niswender C. M., Sanders-Bush E., and Emeson R. B. (1998) Identification and characterization of RNA editing events within the 5-HT2C receptor. Ann. NY Acad. Sci. 861, 38-48.
63. Wang Q., O'Brien P. J., Chen C. X., Cho D. S., Murray J. M., and Nishikura K. (2000) Altered G protein-coupling functions of RNA editing isoform and splicing variant serotonin2C receptors. J. Neurochem. 74, 1290-1300.
64. Englander M. T., Dulawa S. C., Bhansali P., and Schmauss C. (2005) How stress and fluoxetine modulate serotonin 2C receptor pre-MRNA editing. J. Neurosci. 25, 648-651.
65. Gurevich I., Tamir H., Arango V., Dwork A. J., Mann J. J., and Schmauss C. (2002) Altered editing of serotonin 2C receptor pre-MRNA in the prefrontal cortex of depressed suicide victims. Neuron 34, 349-356.
66. Gurevich I., Englander M. T., Adlersberg M., Siegal N. B., and Schmauss C. (2002) Modulation of serotonin 2C receptor editing by sustained changes in serotonergic neurotransmission. J. Neurosci. 22, 10,529-10,532.
67. Heisler L. K., Chu H. M., and Tecott L. H. (1998) Epilepsy and obesity in serotonin 5-HT2C receptor mutant mice. Ann. NY Acad. Sci. 861, 74-78.
68. Nonogaki K., Strack A. M., Dallman M. F., and Tecott L. H. (1998) Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene. Nat. Med. 4, 1152-1156.
69. Vickers S. P., Clifton P. G., Dourish C. T., and Tecott L. H. (1999) Reduced satiating effect of D-fenfluramine in serotonin 5-HT(2C) receptor mutant mice. Psychopharmacology (Berl.) 143, 309-314.
70. Mossner R., Schmitt A., Hennig T., et al. (2004) Quantitation of 5HT3 receptors in forebrain of serotonin transporter deficient mice. J. Neural Trans. 111, 27-35.
71. Chen J. J., Li Z. S., Pan H., et al. (2001) Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-affinity serotonin transporter: abnormal intestinal motility and the expression of cation transporters. J. Neurosci. 21, 6348-6361.
72. Liu M. T., Rayport S., Jiang Y., Murphy D. L., and Gershon M. D. (2002) Expression and function of 5-HT3 receptors in the enteric neurons of mice lacking the serotonin transporter. Am. J. Physiol. Gastrointestinal Liver Physiol. 283, G1398-G1411.
73. Tjurmina O. A., Armando I., Saavedra J. M., Goldstein D. S., and Murphy D. L. (2002) Exaggerated adrenomedullary response to immobilization in mice with targeted disruption of the serotonin transporter gene. Endocrinology 143, 4520-4526.
74. Persico A. M., Mengual E., Moessner R., et al. (2001) Barrel pattern formation requires serotonin uptake by thalamocortical afferents, and not vesicular monoamine release. J. Neurosci. 21, 6862-6873.
75. Salichon N., Gaspar P., Upton A. L., et al. (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.
76. Esaki T., Cook M., Shimoji K., Murphy D. L., Sokoloff L., and Holmes A. (2005) Developmental disruption of serotonin transporter function impairs cerebral responses to whisker stimulation in mice. Proc. Nat. Acad. Sci. USA 102, 5582-5587.
77. Freo U., Ori C., Dam M., Merico A., and Pizzolato G. (2000) Effects of acute and chronic treatment with fluoxetine on regional glucose cerebral metabolism in rats: implications for clinical therapies. Brain Res. 854, 35-41.
78. Azmitia E. C. (2001) Neuronal instability: implications for Rett's syndrome. Brain Develop. 23, S1-S10.
79. Persico A. M., Baldi A., Dell'Acqua M. L., et al. (2003) Reduced programmed cell death in brains of serotonin transporter knockout mice. Neuroreport 14, 341-344.
80. Zhou F. C., Lesch K. P., and Murphy D. L. (2002) Serotonin uptake into dopamine neurons via dopamine transporters: a compensatory alternative. Brain Res. 942, 109-119.
81. Pan Y., Gembom E., Peng W., Lesch K. P., Mossner R., and Simantov R. (2001) Plasticity in serotonin uptake in primary neuronal cultures of serotonin transporter knockout mice. Brain Res. Dev. Brain Res. 126, 125-129.
82. Holmes A., Yang R. J., Murphy D. L., and Crawley J. N. (2002) Evaluation of antidepressant-related behavioral responses in mice lacking the serotonin transporter. Neuropsychopharmacology 27, 914-923.
83. Schmitt A., Mossner R., Gossmann A., et al. (2003) Organic cation transporter capable of transporting serotonin is up-regulated in serotonin transporter-deficient mice. J. Neurosci. Res. 71, 701-709.
84. La Cour C. M., Hanoun N., Melfort M., et al. (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.
85. Mannoury L. C., Hanoun N., Melfort M., et al. (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.
86. Mossner R., Albert D., Persico A. M., et al. (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.
87. Kilic F., Murphy D. L., and Rudnick G. (2003) A human serotonin transporter mutation causes constitutive activation of transport activity. Mol. Pharmacol. 64, 440-446.
88. Ozaki N., Goldman D., Kaye W. H., et al. (2003) Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype. Mol. Psych. 8, 933-936.
89. David S. P., Murthy N. V., Rabiner E. A., et al. (2005) A functional genetic variation of the serotonin (5-HT) transporter affects 5-HT1A receptor binding in humans. J. Neurosci. 25, 2586-2590.