Interest of using genetically manipulated mice as models of depression to evaluate antidepressant drugs activity: a review
Alain M. Gardier,
Bruno P. Guiard,
Jean-Philippe Guilloux,
Christelle Repérant,
François Coudoré,
Denis J. David,
Corresponding Author
Alain M. Gardier
*Correspondence and reprints: [email protected]Search for more papers by this authorBruno P. Guiard
Fac. Pharmacie, Univ. Paris Sud, EA 3544, Chatenay-Malabry cedex F-92296, France
Search for more papers by this authorJean-Philippe Guilloux
Fac. Pharmacie, Univ. Paris Sud, EA 3544, Chatenay-Malabry cedex F-92296, France
Search for more papers by this authorChristelle Repérant
Fac. Pharmacie, Univ. Paris Sud, EA 3544, Chatenay-Malabry cedex F-92296, France
Search for more papers by this authorFrançois Coudoré
Fac. Pharmacie, Univ. Paris Sud, EA 3544, Chatenay-Malabry cedex F-92296, France
Search for more papers by this authorDenis J. David
Fac. Pharmacie, Univ. Paris Sud, EA 3544, Chatenay-Malabry cedex F-92296, France
Search for more papers by this authorAlain M. Gardier,
Bruno P. Guiard,
Jean-Philippe Guilloux,
Christelle Repérant,
François Coudoré,
Denis J. David,
Corresponding Author
Alain M. Gardier
*Correspondence and reprints: [email protected]Search for more papers by this authorBruno P. Guiard
Fac. Pharmacie, Univ. Paris Sud, EA 3544, Chatenay-Malabry cedex F-92296, France
Search for more papers by this authorJean-Philippe Guilloux
Fac. Pharmacie, Univ. Paris Sud, EA 3544, Chatenay-Malabry cedex F-92296, France
Search for more papers by this authorChristelle Repérant
Fac. Pharmacie, Univ. Paris Sud, EA 3544, Chatenay-Malabry cedex F-92296, France
Search for more papers by this authorFrançois Coudoré
Fac. Pharmacie, Univ. Paris Sud, EA 3544, Chatenay-Malabry cedex F-92296, France
Search for more papers by this authorDenis J. David
Fac. Pharmacie, Univ. Paris Sud, EA 3544, Chatenay-Malabry cedex F-92296, France
Search for more papers by this authorAbstract
Among the multiple possibilities to study human depressive disorders, animal models remain important preclinical tools. They allow the understanding of the mechanisms of action of antidepressant drugs. Primarily developed in rat, animal models of depression have been adapted to the mouse, an easy-to-use mammal with better genetic possibilities than rats. As an example, genetic manipulation of the serotoninergic 5-hydroxytryptamine-HT; (5-HT) system provided important opportunities to investigate the role of this monoamine in mood disorders. The contribution of either constitutive knockout (KO), tissue specific, or inducible KO mice and animal models in the current knowledge of the pathophysiology and treatment of depression is unanimously recognized. The phenotype of genetically manipulated animals is strongly influenced by both the genetic background of the animal as well as environmental factors. For these reasons, it is necessary to underline that KO mice have been generated on various genetic backgrounds, which strongly influence the behavioral and neurochemical responses to the tests. The present review will thus focus on KO mice lacking G protein-coupled monoaminergic receptors (e.g; 5-HT1B, 5-HT1A, and 5-HT4 receptors) and the 5-HT serotonin transporter, which is the main target of antidepressant drugs (or strategies). The importance of KO mice for neurotrophic factors, particularly for brain-derived neurotrophic factor and its main receptor displaying a tyrosine kinase activity, will also be addressed to illustrate the fact that in preclinical studies, combination of genetic manipulations with pharmacological ones should allow further progress in the field of neuropsychopharmacology.
References
- 1 Levinson D., Haklai Z., Stein N., Gordon E.S. Suicide attempts in israel: age by gender analysis of a national emergency departments database. Suicide Life Threat. Behav. (2006) 36 97–102.
- 2 Mill J., Petronis A. Molecular studies of major depressive disorder: the epigenetic perspective. Mol. Psychiatry. (2007) 12 799–814.
- 3 Morilak D.A., Frazer A. Antidepressants and brain monoaminergic systems: a dimensional approach to understanding their behavioural effects in depression and anxiety disorders. Int. J. Neuropsychopharmacol. (2004) 7 193–218.
- 4 Katz M.M., Tekell J.L., Bowden C.L. et al. Onset and early behavioral effects of pharmacologically different antidepressants and placebo in depression. Neuropsychopharmacology (2004) 29 566–579.
- 5 Blier P., De Montigny C. Current advances and trends in the treatment of depression. Trends Pharmacol. Sci. (1994) 15 220–226.
- 6 Cryan J.F., Markou A., Lucki I. Assessing antidepressant activity in rodents: recent developments and future needs. Trends Pharmacol. Sci. (2002) 23 238–245.
- 7 Willner P. Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology (Berl) (1997) 134 319–329.
- 8 Willner P. Chronic mild stress (CMS) revisited: consistency and behavioural-neurobiological concordance in the effects of CMS. Neuropsychobiology (2005) 52 90–110.
- 9 El Yacoubi M., Bouali S., Popa D. et al. Behavioral, neurochemical, and electrophysiological characterization of a genetic mouse model of depression. Proc. Natl. Acad. Sci. USA. (2003) 100 6227–6232.
- 10 Silva A.J., Paylor R., Wehner J.M., Tonegawa S. Impaired spatial learning in alpha-calcium-calmodulin kinase II mutant mice. Science (1992) 257 206–211.
- 11 Mayorga A.J., Lucki I. Limitations on the use of the C57BL/6 mouse in the tail suspension test. Psychopharmacology (Berl) (2001) 155 110–112.
- 12 Porsolt R.D., Bertin A., Jalfre M. Behavioral despair in mice: a primary screening test for antidepressants. Arch. Int. Pharmacodyn. Ther. (1977) 229 327–336.
- 13 Steru L., Chermat R., Thierry B., Simon P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology (Berl) (1985) 85 367–370.
- 14 Dulawa S.C., Holick K.A., Gundersen B., Hen R. Effects of chronic fluoxetine in animal models of anxiety and depression. Neuropsychopharmacology (2004) 29 1321–1330.
- 15 David D.J., Klemenhagen K.C., Holick K.A. et al. Efficacy of the MCHR1 antagonist N-[3-(1-{[4-(3,4-difluorophenoxy)phenyl]methyl}(4-piperidyl))-4-methylphenyl]-2-methylpropanamide (SNAP 94847) in mouse models of anxiety and depression following acute and chronic administration is independent of hippocampal neurogenesis. J. Pharmacol. Exp. Ther. (2007) 321 237–248.
- 16 Cohen S., Chang A., Boyer H., Helling R. Construction of biologically functional bacterial plasmids in vitro. Proc. Natl. Acad. Sci. USA. (1973) 70 3240–3244.
- 17 Genentech: Press Releases - News Release September 6, 1978. The insulin synthesis is the first laboratory production DNA technology.
- 18 Evans M.J., Kaufman M.H. Establishment in culture of pluripotential cells from mouse embryos. Nature (1981) 292 154–156.
- 19 Bradley A., Evans M., Kaufman M.H., Robertson E. Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines. Nature (1984) 309 255–256.
- 20 Kuehn M.R., Bradley A., Robertson E.J., Evans M.J. A potential animal model for Lesch-Nyhan syndrome through introduction of HPRT mutations into mice. Nature (1987) 326 295–298.
- 21 Folger K.R., Wong E.A., Wahl G., Capecchi M.R. Patterns of integration of DNA microinjected into cultured mammalian cells: evidence for homologous recombination between injected plasmid DNA molecules. Mol. Cell. Biol. (1982) 2 1372–1387.
- 22 Thomas K.R., Capecchi M.R. Targeted disruption of the murine int-1 proto-oncogene resulting in severe abnormalities in midbrain and cerebellar development. Nature (1990) 346 847–850.
- 23 Canli T., Lesch K.P. Long story short: the serotonin transporter in emotion regulation and social cognition. Nat. Neurosci. (2007) 10 1103–1109.
- 24 Murphy D.L., Lesch K.P. Targeting the murine serotonin transporter: insights into human neurobiology. Nat Rev. Neurosci. (2008) 9 85–96.
- 25 Bengel D., Murphy D.L., Andrews A.M. et al. Altered brain serotonin homeostasis and locomotor insensitivity to 3, 4-methylenedioxymethamphetamine (“Ecstasy”) in serotonin transporter-deficient mice. Mol. Pharmacol. (1998) 53 649–655.
- 26 Lesch K.P., Bengel D., Heils A. et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science (1996) 274 1527–1531.
- 27 Serretti A., Benedetti F., Zanardi R., Smeraldi E. The influence of serotonin transporter promoter polymorphism (SERTPR) and other polymorphisms of the serotonin pathway on the efficacy of antidepressant treatments. Prog. Neuropsychopharmacol. Biol. Psychiatry. (2005) 29 1074–1084.
- 28 Hariri A.R., Mattay V.S., Tessitore A. et al. Serotonin transporter genetic variation and the response of the human amygdala. Science (2002) 297 400–403.
- 29 Caspi A., Sugden K., Moffitt T.E. et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science (2003) 301 386–389.
- 30 Alexandre C., Popa D., Fabre V. et al. Early life blockade of 5-hydroxytryptamine 1A receptors normalizes sleep and depression-like behavior in adult knock-out mice lacking the serotonin transporter. J. Neurosci. (2006) 26 5554–5564.
- 31 Fox M.A., Andrews A.M., Wendland J.R., Lesch K.P., Holmes A., Murphy D.L. A pharmacological analysis of mice with a targeted disruption of the serotonin transporter. Psychopharmacology (Berl) (2007) 195 147–166.
- 32 Mathews T.A., Fedele D.E., Coppelli F.M., Avila A.M., Murphy D.L., Andrews A.M. Gene dose-dependent alterations in extraneuronal serotonin but not dopamine in mice with reduced serotonin transporter expression. J. Neurosci. Methods. (2004) 140 169–181.
- 33 Szapacs M.E., Mathews T.A., Tessarollo L., Ernest Lyons W., Mamounas L.A., Andrews A.M. Exploring the relationship between serotonin and brain-derived neurotrophic factor: analysis of BDNF protein and extraneuronal 5-HT in mice with reduced serotonin transporter or BDNF expression. J. Neurosci. Methods. (2004) 140 81–92.
- 34 Fabre V., Beaufour C., Evrard A. et al. Altered expression and functions of serotonin 5-HT1A and 5-HT1B receptors in knock-out mice lacking the 5-HT transporter. Eur. J. Neurosci. (2000) 12 2299–2310.
- 35 Piñeyro G., Blier P., Dennis T., De Montigny C. Desensitization of the neuronal 5-HT carrier following its long-term blockade. J. Neurosci. (1994) 14 3036–3047.
- 36 Benmansour S., Owens W.A., Cecchi M., Morilak D.A., Frazer A. Serotonin clearance in vivo is altered to a greater extent by antidepressant-induced downregulation of the serotonin transporter than by acute blockade of this transporter. J. Neurosci. (2002) 22 6766–6272.
- 37 Lira A., Zhou M., Castanon N. et al. Altered depression-related behaviors and functional changes in the dorsal raphe nucleus of serotonin transporter-deficient mice. Biol. Psychiatry. (2003) 54 960–971.
- 38 Ansorge M.S., Zhou M., Lira A., Hen R., Gingrich J.A. Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice. Science (2004) 306 879–881.
- 39 Ansorge M.S., Morelli E., Gingrich J.A. Inhibition of serotonin but not norepinephrine transport during development produces delayed, persistent perturbations of emotional behaviors in mice. J. Neurosci. (2008) 28 199–207.
- 40 Pezawas L., Meyer-Lindenberg A., Drabant E.M. et al. 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nat. Neurosci. (2005) 8 828–834.
- 41 Saudou F., Amara D.A., Dierich A. et al. Enhanced aggressive behavior in mice lacking 5-HT1B receptor. Science (1994) 265 1875–1878.
- 42 Snyder S.H. Neurobiology: serotonin sustains serenity. Nature (2002) 416 377–380.
- 43 Artigas F., Romero L., De Montigny C., Blier P. Acceleration of the effect of selected antidepressant drugs in major depression by 5-HT1A antagonists. Trends Neurosci. (1996) 19 378–383.
- 44 Blier P. Pharmacology of rapid-onset antidepressant treatment strategies. J. Clin. Psychiatry. (2001) 62 12–17.
- 45 Rutter J.J., Gundlah C., Auerbach S.B. Systemic uptake inhibition decreases serotonin release via somatodendritic autoreceptor activation. Synapse (1995) 20 225–233.
- 46 Gardier A.M., David D.J., Jego G. et al. Effects of chronic paroxetine treatment on dialysate serotonin in 5-HT1B receptor knockout mice. J. Neurochem. (2003) 86 13–24.
- 47 Ramboz S., Saudou F., Amara D.A. et al. 5-HT1B receptor knock out – behavioral consequences. Behav. Brain Res. (1996) 73 305–312.
- 48 Piñeyro G., Castanon N., Hen R., Blier P. Regulation of [3H]5-HT release in raphe, frontal cortex and hippocampus of 5-HT1B knock-out mice. Neuroreport (1995) 7 353–359.
- 49 Trillat A.C., Malagié I., Scearce K. et al. Regulation of serotonin release in the frontal cortex and ventral hippocampus of homozygous mice lacking 5-HT1B receptors: in vivo microdialysis studies. J. Neurochem. (1997) 69 2019–2025.
- 50 Trillat A.C., Malagié I., Bourin M., Jacquot C., Hen R., Gardier A.M. Homozygote mice deficient in serotonin 5-HT1B receptor and antidepressant effect of selective serotonin reuptake inhibitors. C. R. Seances Soc. Biol. Fil. (1998) 192 1139–1147.
- 51 De Groote L., Olivier B., Westenberg H.G. Extracellular serotonin in the prefrontal cortex is limited through terminal 5-HT(1B) autoreceptors: a microdialysis study in knockout mice. Psychopharmacology (Berl) (2002) 162 419–424.
- 52 Malagié I., Trillat A.C., Bourin M., Jacquot C., Hen R., Gardier A.M. 5-HT1B Autoreceptors limit the effects of selective serotonin re-uptake inhibitors in mouse hippocampus and frontal cortex. J. Neurochem. (2001) 76 865–871.
- 53 El Mansari M., Blier P. Functional characterization of 5-HT1D autoreceptors on the modulation of 5-HT release in guinea-pig mesencephalic raphe, hippocampus and frontal cortex. Br. J. Pharmacol. (1996) 118 681–689.
- 54 Jones M.D., Lucki I. Sex differences in the regulation of serotonergic transmission and behavior in 5-HT receptor knockout mice. Neuropsychopharmacology (2005) 30 1039–1047.
- 55 Shippenberg T.S., Hen R., He M. Region-specific enhancement of basal extracellular and cocaine-evoked dopamine levels following constitutive deletion of the Serotonin(1B) receptor. J. Neurochem. (2000) 75 258–265.
- 56 Ase A.R., Sénécal J., Reader T.A., Hen R., Descarries L. Decreased G-protein coupling of serotonin 5-HT(1A) receptors in the brain of 5-HT(1B) knockout mouse. Neuropharmacology (2002) 42 941–949.
- 57 Gardier A.M., Gruwez B., Trillat A.C., Jacquot C., Hen R., Bourin M. Interaction between 5-HT(1A) and 5-HT(1B) receptors: effects of 8-OH-DPAT-induced hypothermia in 5-HT(1B) receptor knockout mice. Eur. J. Pharmacol. (2001) 421 171–175.
- 58 Bouwknecht J.A., Hijzen T.H., Van Der Gugten J. et al. Startle responses, heart rate, and temperature in 5-HT1B receptor knockout mice. Neuroreport. (2000) 11 4097–4102.
- 59 Clifton P.G., Lee M.D., Somerville E.M., Kennett G.A., Dourish C.T. 5-HT1B receptor knockout mice show a compensatory reduction in 5-HT2C receptor function. Eur. J. Neurosci. (2003) 17 185–190.
- 60 Groenink L., Van Bogaert M.J., Van Der Gugten J., Oosting R.S., Olivier B. 5-HT1A receptor and 5-HT1B receptor knockout mice in stress and anxiety paradigms. Behav. Pharmacol. (2003) 14 369–383.
- 61 Artigas F. 5-HT and antidepressants: new views from microdialysis studies. Trends Pharmacol. Sci. (1993) 14 262.
- 62 Julius D. Serotonin receptor knockouts: a moody subject. Proc. Natl. Acad. Sci. USA. (1998) 95 15153–15154.
- 63 Toth M. 5-HT1A receptor knockout mouse as a genetic model of anxiety. Eur. J. Pharmacol. (2003) 463 177–184.
- 64 Parks C.L., Robinson P.S., Sibille E., Shenk T., Toth M. Increased anxiety of mice lacking the serotonin1A receptor. Proc. Natl. Acad. Sci. USA. (1998) 95 10734–10739.
- 65 Ramboz S., Oosting R., Amara D.A. et al. Serotonin receptor 1A knockout: an animal model of anxiety-related disorder. Proc Natl Acad Sci U S A. (1998) 95 14476–14481.
- 66 Heisler L.K., Chu H.M., Brennan T.J. et al. Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor mutant mice. Proc. Natl. Acad. Sci. USA. (1998) 95 15049–15054.
- 67 Gross C., Zhuang X., Stark K. et al. Serotonin1A receptor acts during development to establish normal anxiety-like behaviour in the adult. Nature (2002) 416 396–400.
- 68 Bortolozzi A., Amargós-Bosch M., Toth M., Artigas F., Adell A. In vivo efflux of serotonin in the dorsal raphe nucleus of 5-HT1A receptor knockout mice. J. Neurochem. (2004) 88 1373–1379.
- 69 Guilloux J.P., David D.J., Guiard B.P. et al. Blockade of 5-HT1A receptors by (+/−)-pindolol potentiates cortical 5-HT outflow, but not antidepressant-like activity of paroxetine: microdialysis and behavioral approaches in 5-HT1A receptor knockout mice. Neuropsychopharmacology (2006) 31 2162–2172.
- 70 Sibille E., Pavlides C., Benke D., Toth M. Genetic inactivation of the Serotonin(1A) receptor in mice results in downregulation of major GABA(A) receptor alpha subunits, reduction of GABA(A) receptor binding, and benzodiazepine-resistant anxiety. J. Neurosci. (2000) 20 2758–2765.
- 71 Ballesteros J., Callado L.F. Effectiveness of pindolol plus serotonin uptake inhibitors in depression: a meta-analysis of early and late outcomes from randomised controlled trials. J. Affect. Disord. (2004) 79 137–147.
- 72 Malberg J.E., Eisch A.J., Nestler E.J., Duman R.S. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J. Neurosci. (2000) 20 9104–9110.
- 73 Duman R.S., Malberg J., Nakagawa S. Regulation of adult neurogenesis by psychotropic drugs and stress. J. Pharmacol. Exp. Ther. (2001) 299 401–407.
- 74 Santarelli L., Saxe M., Gross C. et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science (2003) 301 805–809.
- 75 Holick K.A., Lee D.C., Hen R., Dulawa S.C. Behavioral effects of chronic fluoxetine in BALB/cJ mice do not require adult hippocampal neurogenesis or the serotonin 1A receptor. Neuropsychopharmacology (2008) 33 406–417.
- 76 Vollmayr B., Simonis C., Weber S., Gass P., Henn F. Reduced cell proliferation in the dentate gyrus is not correlated with the development of learned helplessness. Biol. Psychiatry. (2003) 54 1035–1040.
- 77 Sahay A., Hen R. Adult hippocampal neurogenesis in depression. Nat. Neurosci. (2007) 10 1110–1115.
- 78 Schmidt H.D., Duman R.S. The role of neurotrophic factors in adult hippocampal neurogenesis, antidepressant treatments and animal models of depressive-like behavior. Behav. Pharmacol. (2007) 18 391–418.
- 79 Cunningham K.A., Watson C.S. Cell cycle regulation, neurogenesis, and depression. Proc. Natl. Acad. Sci. USA. (2008) 105 2259–2260.
- 80 Boutrel B., Monaca C., Hen R., Hamon M., Adrien J. Involvement of 5-HT1A receptors in homeostatic and stress-induced adaptive regulations of paradoxical sleep: studies in 5-HT1A knock-out mice. J. Neurosci. (2002) 22 4686–4692.
- 81 Sarnyai Z., Sibille E.L., Pavlides C., Fenster R.J., McEwen B.S., Toth M. Impaired hippocampal-dependent learning and functional abnormalities in the hippocampus in mice lacking serotonin(1A) receptors. Proc. Natl. Acad. Sci. USA. (2000) 97 14731–1476.
- 82 Compan V., Zhou M., Grailhe R. et al. Attenuated response to stress and novelty and hypersensitivity to seizures in 5-HT4 receptor knock-out mice. J. Neurosci. (2004) 24 412–419.
- 83 Conductier G., Dusticier N., Lucas G. et al. Adaptive changes in serotonin neurons of the raphe nuclei in 5-HT(4) receptor knock-out mouse. Eur. J. Neurosci. (2006) 24 1053–1062.
- 84 Lucas G., Rymar V.V., Du J. et al. Serotonin(4) (5-HT(4)) receptor agonists are putative antidepressants with a rapid onset of action. Neuron (2007) 55 712–725.
- 85 Ducottet C., Aubert A., Belzung C. Susceptibility to subchronic unpredictable stress is related to individual reactivity to threat stimuli in mice. Behav. Brain Res. (2004) 155 291–299.
- 86 Gage F.H., Ray J., Fisher L.J. Isolation, characterization, and use of stem cells from the CNS. Annu. Rev. Neurosci. (1995) 18 159–192.
- 87 Cameron H.A., Gould E. Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus. Neuroscience (1994) 61 203–209.
- 88 Gould E. How widespread is adult neurogenesis in mammals? Nat. Rev. Neurosci. (2007) 8 481–488.
- 89 Wang J.W., David D.J., Monckton J.E., Battaglia F., Hen R. Chronic fluoxetine stimulates maturation and synaptic plasticity of adult-born hippocampal granule cells. J. Neurosci. (2008) 28 1374–1384.
- 90 Duman R.S., Malberg J., Thome J. Neural plasticity to stress and antidepressant treatment. Biol. Psychiatry. (1999) 46 1181–1191.
- 91 Dwivedi Y., Rizavi H.S., Pandey G.N. Antidepressants reverse corticosterone-mediated decrease in brain-derived neurotrophic factor expression: differential regulation of specific exons by antidepressants and corticosterone. Neuroscience (2006) 139 1017–1029.
- 92 Shirayama Y., Chen A.C., Nakagawa S., Russell D.S., Duman R.S. Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. J. Neurosci. (2002) 22 3251–3261.
- 93 Sheline Y.I., Wang P.W., Gado M.H., Csernansky J.G., Vannier M.W. Hippocampal atrophy in recurrent major depression. Proc. Natl. Acad. Sci. USA. (1996) 93 3908–3913.
- 94 Nibuya M., Morinobu S., Duman R.S. Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J. Neurosci. (1995) 15 7539–7547.
- 95 Nibuya M., Nestler E.J., Duman R.S. Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus. J. Neurosci. (1996) 7 2365–2372.
- 96 Rantamäki T., Hendolin P., Kankaanpää A. et al. Pharmacologically diverse antidepressants rapidly activate brain-derived neurotrophic factor receptor TrkB and induce phospholipase-Cgamma signaling pathways in mouse brain. Neuropsychopharmacology (2007) 32 2152–2162.
- 97 Mattson M.P., Maudsley S., Martin B. BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders. Trends Neurosci. (2004) 27 589–594.
- 98 Mamounas L.A., Altar C.A., Blue M.E., Kaplan D.R., Tessarollo L., Lyons W.E. BDNF promotes the regenerative sprouting, but not survival, of injured serotonergic axons in the adult rat brain. J. Neurosci. (2000) 20 771–782.
- 99 Ernfors P., Lee K.F., Jaenisch R. Mice lacking brain-derived neurotrophic factor develop with sensory deficits. Nature (1994) 368 147–150.
- 100 Korte M., Carroll P., Wolf E., Brem G., Thoenen H., Bonhoeffer T. Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor. Proc. Natl. Acad. Sci. USA. (1995) 92 8856–8860.
- 101 Saarelainen T., Hendolin P., Lucas G. et al. Activation of the TrkB neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant-induced behavioral effects. J. Neurosci. (2003) 23 349–357.
- 102 Sairanen M., Lucas G., Ernfors P., Castrén M., Castrén E. Brain-derived neurotrophic factor and antidepressant drugs have different but coordinated effects on neuronal turnover, proliferation, and survival in the adult dentate gyrus. J. Neurosci. (2005) 25 1089–1094.
- 103 Lyons W.E., Mamounas L.A., Ricaurte G.A. et al. Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities. Proc. Natl. Acad. Sci. USA. (1999) 96 15239–15244.
- 104 Lee J., Seroogy K.B., Mattson M.P. Dietary restriction enhances neurotrophin expression and neurogenesis in the hippocampus of adult mice. J. Neurochem. (2002) 80 539–547.
- 105 Guiard B.P., David D.J., Deltheil T. et al. Brain-derived neurotrophic factor-deficient mice exhibit a hippocampal hyperserotonergic phenotype. Int. J. Neuropsychopharmacol. (2008) 11 79–92.
- 106 Daws L.C., Munn J.L., Valdez M.F., Frosto-Burke T., Hensler J.G. Serotonin transporter function, but not expression, is dependent on brain-derived neurotrophic factor (BDNF): in vivo studies in BDNF-deficient mice. J. Neurochem. (2007) 101 641–651.
- 107 Benmansour S., Deltheil T., Piotrowski J. et al. Influence of brain-derived neurotrophic factor (BDNF) on serotonin neurotransmission in the hippocampus of adult rodents. Eur. J. Pharmacol. (2008) 587 90–98.
- 108 Luellen B.A., Bianco L.E., Schneider L.M., Andrews A.M. Reduced brain-derived neurotrophic factor is associated with a loss of serotonergic innervation in the hippocampus of aging mice. Genes. Brain. Behav. (2007) 6 482–490.
- 109 Aiba A., Nakao H. Conditional mutant mice using tetracycline-controlled gene expression system in the brain. Neurosci. Res. (2007) 58 113–117.
- 110 Rios M., Fan G., Fekete C. et al. Conditional deletion of brain-derived neurotrophic factor in the postnatal brain leads to obesity and hyperactivity. Mol. Endocrinol. (2001) 15 1748–1757.
- 111 Berton O., McClung C.A., Dileone R.J. et al. Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science (2006) 311 864–868.
- 112 Adachi M., Barrot M., Autry A.E., Theobald D., Monteggia L.M. Selective loss of brain-derived neurotrophic factor in the dentate gyrus attenuates antidepressant efficacy. Biol. Psychiatry. (2008) 63 642–649.
- 113 Monteggia L.M., Barrot M., Powell C.M. et al. Essential role of brain-derived neurotrophic factor in adult hippocampal function. Proc. Natl. Acad. Sci. USA. (2004) 101 10827–10832.
- 114 Wang J.W., Dranovsky A., Hen R. The when and where of BDNF and the antidepressant response. Biol. Psychiatry. (2008) 63 640–641.
- 115 Deltheil T., Nicolas L., Cerdan J. et al. Consequences of altered brain-derived neurotrophic factor protein levels on hippocampal serotonin neurotransmission and behavior. Pharmacol. Biochem. Behav. (2008) 90 174–183.
- 116 Monteggia L.M., Luikart B., Barrot M. et al. Brain-derived neurotrophic factor conditional knockouts show gender differences in depression-related behaviors. Biol. Psychiatry. (2007) 61 187–197.
- 117 Pröschel M., Saunders A., Roses A.D., Müller C.R. Dinucleotide repeat polymorphism at the human gene for the brain-derived neurotrophic factor (BDNF). Hum. Mol. Genet. (1992) 1 353.
- 118 Egan M.F., Kojima M., Callicott J.H. et al. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell. (2003) 112 257–269.
- 119 Chen Z.Y., Jing D., Bath K.G. et al. Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. Science (2006) 314 140–143.
- 120 Heurteaux C., Lucas G., Guy N. et al. Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype. Nat. Neurosci. (2006) 9 1134–1141.
- 121 Bouwknecht J.A., Van Der Gugten J., Hijzen T.H., Maes R.A., Hen R., Olivier B. Corticosterone responses in 5-HT1B receptor knockout mice to stress or 5-HT1A receptor activation are normal. Psychopharmacology (2001) 153 484–490.
- 122 Knobelman D.A., Hen R., Lucki I. Genetic regulation of extracellular serotonin by 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B) autoreceptors in different brain regions of the mouse. J. Pharmacol. Exp. Ther. (2001) 298 1083–1091.
- 123 Mayorga A.J., Dalvi A., Page M.E., Zimov-Levinson S., Hen R., Lucki I. Antidepressant-like behavioral effects in 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B) receptor mutant mice. J. Pharmacol. Exp. Ther. (2001) 298 1101–1107.
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