Antidepressant and anxiolytic potential of the multimodal antidepressant vortioxetine (Lu AA21004) assessed by behavioural and neurogenesis outcomes in mice

Neuropharmacology

Volumn 73, Issue , 2013, Pages 147-159

  Guilloux, Jean Philippe ^a   Mendez David, Indira ^a   Alan, Pehrson ^b   Guiard, Bruno P ^a   Repérant, Christelle ^a   Orvoën, Sophie ^a   Gardier, Alain M ^a   Hen, René ^d   Bjarke, Ebert ^c   Silke, Miller ^b,e   Connie, Sanchez ^b   David, Denis J ^a  

^a University of Paris XI   (France)

^b LUNDBECK RESEARCH USA   (United States)

^c H LUNDBECK A S   (Denmark)

^d Och Spine at New York Presbyterian Hospitals   (United States)

^e AMGEN INC   (United States)

Author keywords

Antidepressant; Anxiolytic; Behaviour; Mice; Multimodal antidepressant; Neurogenesis

Indexed keywords

DIAZEPAM; FLUOXETINE; SEROTONIN 3 RECEPTOR; SEROTONIN TRANSPORTER; VORTIOXETINE;

129 MOUSE; ADULT ANIMAL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTIDEPRESSANT ACTIVITY; ARTICLE; BAGG ALBINO MOUSE; CELL MATURATION; CELL PROLIFERATION; CELL SURVIVAL; CHRONIC DRUG ADMINISTRATION; CONTROLLED STUDY; DENDRITE; DENTATE GYRUS; FORCED SWIMMING TEST; GRANULE CELL; MALE; MOUSE; NERVOUS SYSTEM DEVELOPMENT; NONHUMAN; OPEN FIELD TEST; PRIORITY JOURNAL; RECEPTOR OCCUPANCY; TRANQUILIZING ACTIVITY;

ANTIDEPRESSANT; ANXIOLYTIC; BEHAVIOUR; MICE; MULTIMODAL ANTIDEPRESSANT; NEUROGENESIS;

ANIMALS; ANTI-ANXIETY AGENTS; ANTIDEPRESSIVE AGENTS; DENTATE GYRUS; DIAZEPAM; DRUG EVALUATION, PRECLINICAL; EXPLORATORY BEHAVIOR; FLUOXETINE; IMMOBILITY RESPONSE, TONIC; MALE; MICE; MOTOR ACTIVITY; NEUROGENESIS; PIPERAZINES; SULFIDES;

EID: 84885163818     PISSN: 00283908     EISSN: 18737064     Source Type: Journal    
DOI: 10.1016/j.neuropharm.2013.05.014     Document Type: Article

References (66)

1. Airan, R.D., Meltzer, L.A., Roy, M., Gong, Y., Chen, H., Deisseroth, K., 2007. High-speed imaging reveals neurophysiological links to behavior in an animal model of depression. Science 317, 819-823. (Pubitemid 47257922)
2. Areberg, J., Luntang-Jensen, M., Sogaard, B., Nilausen, D.O., 2012. Occupancy of the serotonin transporter after administration of Lu AA21004 and its relation to plasma concentration in healthy subjects. Basic Clin. Pharmacol. Toxicol. 110, 401-404.
3. Artigas, F., Adell, A., Celada, P., 2006. Pindolol augmentation of antidepressant response. Curr. Drug Targets 7, 139-147.
4. Bailey, J.E., Potokar, J., Coupland, N., Nutt, D.J., 1995. The 5-HT3 antagonist ondansetron reduces gastrointestinal side effects induced by a specific serotonin reuptake inhibitor in man. J. Psychopharmacol. (Oxf.) 9, 137-141.
5. Banasr, M., Hery, M., Printemps, R., Daszuta, A., 2004. Serotonin-induced increases in adult cell proliferation and neurogenesis are mediated through different and common 5-HT receptor subtypes in the dentate gyrus and the subventricular zone. Neuropsychopharmacology 29, 450-460. (Pubitemid 38365922)
6. Bang-Andersen, B., Ruhland, T., Jorgensen, M., Smith, G., Frederiksen, K., Jensen, K.G., Zhong, H., Nielsen, S.M., Hogg, S., Mork, A., Stensbol, T.B., 2011. Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J. Med. Chem. 54, 3206-3221.
7. Barrett, J.E., Gleeson, S., 1991. Anxiolytic effects of 5-HT1A agonists, 5-HT3 antagonists and benzodiazepines: conflict and drug discrimination studies. In: Rogers, R.J., Cooper, S.J. (Eds.), 5-HT1A Agonists, 5-HT3 Antagonists and Benzodiazepines: Their Comparative Behavioural Pharmacology. Wiley & Sons Ltd, Chichester, pp. 59-105.
8. Belzung, C, Griebel, G., 2001. Measuring normal and pathological anxiety-like behaviour in mice: a review. Behav. Brain Res. 125, 141-149. (Pubitemid 33000452)
9. Bespalov, A.Y., van Gaalen, M.M., Gross, G., 2010. Antidepressant treatment in anxiety disorders. Curr. Top. Behav. Neurosci. 2, 361-390.
10. Bonaventure, P., Kelly, L, Aluisio, L., Shelton, J., Lord, B., Galici, R., Miller, K., Atack, J., Lovenberg, T.W., Dugovic, C, 2007. Selective blockade of 5-hydroxytryptamine (5-HT)7 receptors enhances 5-HT transmission, antidepressant-like behavior, and rapid eye movement sleep suppression induced by citalopram in rodents. J. Pharmacol. Exp. Ther. 321, 690-698. (Pubitemid 46624521)
11. Caccia, S., Cappi, M., Fracasso, C, Garattini, S., 1990. Influence of dose and route of administration on the kinetics of fluoxetine and its metabolite norfluoxetine in the rat. Psychopharmacology (Berl.) 100, 509-514. (Pubitemid 20102360)
12. Cervo, L., Canetta, A., Calcagno, E., Burbassi, S., Sacchetti, G., Caccia, S., Fracasso, C, Albani, D., Forloni, G., Invernizzi, R.W., 2005. Genotype-dependent activity of tryptophan hydroxylase-2 determines the response to citalopram in a mouse model of depression. J. Neurosci. 25, 8165-8172. (Pubitemid 41292111)
13. Costall, B., Naylor, R.J., 2004. 5-HT3 receptors. Current drug targets. CNS Neurol. Disord. 3, 27-37.
14. Dagyte, G., Trentani, A., Postema, F., Luiten, P.G., Den Boer, J.A., Gabriel, C, Mocaer, E., Meerlo, P., Van der Zee, E.A., 2010. The novel antidepressant agomelatine normalizes hippocampal neuronal activity and promotes neurogenesis in chronically stressed rats. CNS Neurosci. Ther. 16, 195-207.
15. David, D.J., Klemenhagen, K.C., Holick, K.A., Saxe, M.D., Mendez, I., Santarelli, L., Craig, D.A., Zhong, H., Swanson, C.J., Hegde, LG., Ping, X.I., Dong, D., Marzabadi, M.R., Gerald, C.P., Hen, R., 2007. Efficacy of the MCHR1 antagonist N-[3-(1-{[4-(3,4-difluorophenoxy)phenyl]methyl}(4-piperidyl))-4- methylphenyl]-2-m ethylpropanamide (SNAP 94847) in mouse models of anxiety and depression following acute and chronic administration is independent of hippocampal neurogenesis. J. Pharmacol. Exp. Ther. 321, 237-248. (Pubitemid 46456989)
16. David, D.J., Samuels, B.A., Rainer, Q., Wang, J.W., Marsteller, D., Mendez, I., Drew, M., Craig, DA, Guiard, B.P., Guilloux, J.P., Artymyshyn, R.P., Gardier, A.M., Gerald, C, Antonijevic, I.A., Leonardo, E.D., Hen, R., 2009. Neurogenesis-dependent and -independent effects of fluoxetine in an animal model of anxiety/depression. Neuron 62, 479-493.
17. Dulawa, S.C., Holick, K.A., Gundersen, B., Hen, R., 2004. Effects of chronic fluoxetine in animal models of anxiety and depression. Neuropsychopharmacology 29, 1321-1330. (Pubitemid 38780655)
18. Duman, R.S., Malberg, J., Thome, J., 1999. Neural plasticity to stress and antidepressant treatment. Biol. Psychiatry 46, 1181-1191. (Pubitemid 30114436)
19. Faure, C, Mnie-Filali, O., Scarna, H., Debonnel, G., Haddjeri, N., 2006. Effects of the 5-HT7 receptor antagonist SB-269970 on rat hormonal and temperature responses to the 5-HT1A/7 receptor agonist 8-OH-DPAT. Neurosci. Lett. 404, 122-126. (Pubitemid 44041780)
20. Franklin, K.B.J., Paxinos, G., 2008. The Mouse Brain in Stereotaxic Coordinates. Academic Press, Amsterdam; Boston.
21. Gardier, A.M., Trillat, A.C., Malagie, I., David, D., Hascoet, M., Colombel, M.C., Jolliet, P., Jacquot, C, Hen, R., Bourin, M., 2001. [5-HT1B serotonin receptors and antidepressant effects of selective serotonin reuptake inhibitors]. C. R. Acad. Sci. III 324, 433-441. (Pubitemid 32479477)
22. Gingrich, J.A., Hen, R., 2001. Dissecting the role of the serotonin system in neuropsychiatric disorders using knockout mice. Psychopharmacology (Berl.) 155, 1-10. (Pubitemid 32295763)
23. Guilloux, J.P., David, D.J., Guiard, B.P., Chenu, F., Reperant, C, Toth, M., Bourin, M., Gardier, A.M., 2006. 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 31, 2162-2172. (Pubitemid 44413193)
24. Guilloux, J.P., David, D.J., Xia, L., Nguyen, H.T., Rainer, Q., Guiard, B.P., Reperant, C, Deltheil, T., Toth, M., Hen, R., Gardier, A.M., 2011. Characterization of 5-HT(1A/1B)-/- mice: an animal model sensitive to anxiolytic treatments. Neuropharmacology 61, 478-488.
25. Guilloux, J.P., David, D.J., Samuels, B.A., David, I., Gardier, A.M., Guiard, B.P., 2012. Non-response to Initial Antidepressant Therapy. Psychology. InTech, Rijeka, Croatia.
26. Guscott, M., Bristow, L.J., Hadingham, K., Rosahl, T.W., Beer, M.S., Stanton, J.A., Bromidge, F., Owens, A.P., Huscroft, I., Myers, J., Rupniak, N.M., Patel, S., Whiting, P.J., Hutson, P.H., Fone, K.C., Biello, S.M., Kulagowski, J.J., McAllister, G., 2005. Genetic knockout and pharmacological blockade studies of the 5-HT7 receptor suggest therapeutic potential in depression. Neuropharmacology 48, 492-502. (Pubitemid 40332407)
27. Hamon, M., Bourgoin, S., 2006. Pharmacological profile of antidepressants: a likely basis for their efficacy and side effects? Eur. Neuropsychopharmacol. 16, S625-S632. (Pubitemid 44550176)
28. Hedlund, P.B., Huitron-Resendiz, S., Henriksen, S.J., Sutcliffe, J.G., 2005. 5-HT7 receptor inhibition and inactivation induce antidepressantlike behavior and sleep pattern. Biol. Psychiatry 58, 831-837. (Pubitemid 41677422)
29. Holmes, A., Rodgers, R.J., 2003. Prior exposure to the elevated plus-maze sensitizes mice to the acute behavioral effects of fluoxetine and phenelzine. Eur. J. Pharmacol. 459, 221-230. (Pubitemid 36078325)
30. Kennedy, S.H., Young, A.H., Blier, P., 2011. Strategies to achieve clinical effectiveness: refining existing therapies and pursuing emerging targets. J. Affect. Disord. 132 (Suppl. 1), S21eS28.
31. Kempermann, G., Kuhn, H.G., Gage, F.H., 1997. Genetic influence on neurogenesis in the dentate gyrus of adult mice. Proc. Natl. Acad. Sci. U. S. A. 94, 10409-10414. (Pubitemid 27407055)
32. Kessler, R.C., Berglund, P., Demler, O., Jin, R., Merikangas, K.R., Walters, E.E., 2005. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch. Gen. Psychiatry 62, 593-602. (Pubitemid 40973434)
33. Klempin, F., Babu, H., De Pietri Tonelli, D., Alarcon, E., Fabel, K., Kempermann, G., 2010. Oppositional effects of serotonin receptors 5-HT1a, 2, and 2c in the regulation of adult hippocampal neurogenesis. Front. Mol. Neurosci. 3.
34. Kulikov, A.V., Tikhonova, M.A., Osipova, D.V., Kulikov, V.A., Popova, N.K., 2011. Association between tryptophan hydroxylase-2 genotype and the antidepressant effect of citalopram and paroxetine on immobility time in the forced swim test in mice. Pharmacol. Biochem. Behav. 99, 683-687.
35. Lucki, I., Dalvi, A., Mayorga, A.J., 2001. Sensitivity to the effects of pharmacologically selective antidepressants in different strains of mice. Psychopharmacology (Berl.) 155, 315-322. (Pubitemid 32477289)
36. Malberg, J.E., Eisch, A.J., Nestler, E.J., Duman, R.S., 2000. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J. Neurosci. 20, 9104-9110. (Pubitemid 32042912)
37. Martiny, K., Lunde, M., Bech, P., Plenge, P., 2012. A short-term double-blind randomized controlled pilot trial with active or placebo pindolol in patients treated with venlafaxine for major depression. Nord. J. Psychiatry 66, 147-154.
38. Mnie-Filali, O., Faure, C., Lambas-Senas, L., El Mansari, M., Belblidia, H., Gondard, E., Etievant, A., Scarna, H., Didier, A., Berod, A., Blier, P., Haddjeri, N., 2011. Pharmacological blockade of 5-HT7 receptors as a putative fast acting antidepressant strategy. Neuropsychopharmacology 36, 1275-1288.
39. Mork, A., Pehrson, A., Brennum, L.T., Nielsen, S.M., Zhong, H., Lassen, A.B., Miller, S., Westrich, L., Boyle, N.J., Sanchez, C., Fischer, C.W., Liebenberg, N., Wegener, G., Bundgaard, C., Hogg, S., Bang-Andersen, B., Stensbol, T.B., 2012. Pharmacological effects of Lu AA21004: a novel multimodal compound for the treatment of major depressive disorder. J. Pharmacol. Exp. Ther. 340, 666-675.
40. Mullins, U.L., Gianutsos, G., Eison, A.S., 1999. Effects of antidepressants on 5-HT7 receptor regulation in the rat hypothalamus. Neuropsychopharmacology 21, 352-367. (Pubitemid 29333073)
41. Nishi, K., Kanemaru, K., Diksic, M., 2009. A genetic rat model of depression, Flinders sensitive line, has a lower density of 5-HT(1A) receptors, but a higher density of 5-HT(1B) receptors, compared to control rats. Neurochem. Int. 54, 299-307.
42. Owens, M.J., Morgan, W.N., Plott, S.J., Nemeroff, C.B., 1997. Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites. J. Pharmacol. Exp. Ther. 283, 1305-1322. (Pubitemid 28016506)
43. Pehrson, A.L., Cremers, T., Betry, C., van der Hart, M.G., Jorgensen, L., Madsen, M., Haddjeri, N., Ebert, B., Sanchez, C., 2012. Lu AA21004, a novel multimodal antidepressant, produces regionally selective increases of multiple neurotransmitters-A rat microdialysis and electrophysiology study. Eur. Neuropsychopharmacol. 23 (2), 133-145.
44. Petit-Demouliere, B., Chenu, F., Bourin, M., 2005. Forced swimming test in mice: a review of antidepressant activity. Psychopharmacology (Berl.) 177, 245-255. (Pubitemid 40137284)
45. Popa, D., Cerdan, J., Reperant, C., Guiard, B.P., Guilloux, J.P., David, D.J., Gardier, A.M., 2010. A longitudinal study of 5-HT outflow during chronic fluoxetine treatment using a new technique of chronic microdialysis in a highly emotional mouse strain. Eur. J. Pharmacol. 628, 83-90.
46. Porsolt, R.D., Bertin, A., Jalfre, M., 1977. Behavioral despair in mice: a primary screening test for antidepressants. Arch. Int. Pharmacodyn. Ther. 229, 327-336. (Pubitemid 8225714)
47. Radley, J.J., Jacobs, B.L., 2002. 5-HT1A receptor antagonist administration decreases cell proliferation in the dentate gyrus. Brain Res. 955, 264-267. (Pubitemid 35284859)
48. Rainer, Q., Xia, L., Guilloux, J.P., Gabriel, C., Mocaer, E., Hen, R., Enhamre, E., Gardier, A.M., David, D.J., 2012. Beneficial behavioural and neurogenic effects of agomelatine in a model of depression/anxiety. Int. J. Neuropsychopharmacol. 15, 321-335.
49. Ramamoorthy, R., Radhakrishnan, M., Borah, M., 2008. Antidepressant-like effects of serotonin type-3 antagonist, ondansetron: an investigation in behaviour-based rodent models. Behav. Pharmacol. 19, 29-40.
50. Redrobe, J.P., Bourin, M., 1997. Partial role of 5-HT2 and 5-HT3 receptors in the activity of antidepressants in the mouse forced swimming test. Eur. J. Pharmacol. 325, 129-135. (Pubitemid 27199561)
51. *D report. Am. J. Psychiatry 163, 1905-1917. (Pubitemid 44807782)
52. Sahay, A., Scobie, K.N., Hill, A.S., O'Carroll, C.M., Kheirbek, M.A., Burghardt, N.S., Fenton, A.A., Dranovsky, A., Hen, R., 2011. Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature 472, 466-470.
53. Samuels, B.A., Hen, R., 2012. Novelty-suppressed feeding in the mouse. In: Gould, T.D. (Ed.), Mood and Anxiety Related Phenotypes in Mice. Characterization Using Behavioral Tests. Springer, pp. 107-121.
54. Santarelli, L., Saxe, M., Gross, C., Surget, A., Battaglia, F., Dulawa, S., Weisstaub, N., Lee, J., Duman, R., Arancio, O., Belzung, C., Hen, R., 2003. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 301, 805-809. (Pubitemid 36962615)
55. Sarkisyan, G., Roberts, A.J., Hedlund, P.B., 2010. The 5-HT(7) receptor as a mediator and modulator of antidepressant-like behavior. Behav. Brain Res. 209, 99-108.
56. Soumier, A., Banasr, M., Goff, L.K., Daszuta, A., 2010. Region- and phase-dependent effects of 5-HT(1A) and 5-HT(2C) receptor activation on adult neurogenesis. Eur. Neuropsychopharmacol. 20, 336-345.
57. Soumier, A., Banasr, M., Lortet, S., Masmejean, F., Bernard, N., Kerkerian-Le-Goff, L., Gabriel, C., Millan, M.J., Mocaer, E., Daszuta, A., 2009. Mechanisms contributing to the phase-dependent regulation of neurogenesis by the novel antidepressant, agomelatine, in the adult rat hippocampus. Neuropsychopharmacology 34, 2390-2403.
58. Wang, J.W., David, D.J., Monckton, J.E., Battaglia, F., Hen, R., 2008. Chronic fluoxetine stimulates maturation and synaptic plasticity of adult-born hippocampal granule cells. J. Neurosci. 28, 1374-1384. (Pubitemid 351231535)
59. Wegener, G., Finger, B.C., Elfving, B., Keller, K., Liebenberg, N., Fischer, C.W., Singewald, N., Slattery, D.A., Neumann, I.D., Mathe, A.A., 2011. Neuropeptide S alters anxiety, but not depression-like behaviour in Flinders Sensitive Line rats: a genetic animal model of depression. Int. J. Neuropsychopharmacol., 1-13.
60. Wesolowska, A., Nikiforuk, A., Stachowicz, K., 2006a. Potential anxiolytic and antidepressant effects of the selective 5-HT7 receptor antagonist SB 269970 after intrahippocampal administration to rats. Eur. J. Pharmacol. 553, 185-190. (Pubitemid 44779615)
61. Wesolowska, A., Nikiforuk, A., Stachowicz, K., Tatarczynska, E., 2006b. Effect of the selective 5-HT7 receptor antagonist SB 269970 in animal models of anxiety and depression. Neuropharmacology 51, 578-586. (Pubitemid 44215962)
62. Westrich, L., Pehrson, A., Zhong, H., Nielsen, S.M., Frederiksen, K., Stensbøl, T.B., Boyle, N., Hentzer, M., Sanchez, C., 2012. In vitro and in vivo effects of the multimodal antidepressant vortioxetine (Lu AA21004) at human and rat targets. Int. J. Psychiatry Clin. Pract. 16 (Suppl. 1), 47.
63. Whale, R., Terao, T., Cowen, P., Freemantle, N., Geddes, J., 2010. Pindolol augmentation of serotonin reuptake inhibitors for the treatment of depressive disorder: a systematic review. J. Psychopharmacol. (Oxf.) 24, 513-520.
64. Xia, L., Delomenie, C., David, I., Rainer, Q., Marouard, M., Delacroix, H., David, D.J., Gardier, A.M., Guilloux, J.P., 2012. Ventral hippocampal molecular pathways and impaired neurogenesis associated with 5-HT(1)A and 5-HT(1)B receptors disruption in mice. Neurosci. Lett. 521, 20-25.
65. Zhang, X., Beaulieu, J.M., Sotnikova, T.D., Gainetdinov, R.R., Caron, M.G., 2004. Tryptophan hydroxylase-2 controls brain serotonin synthesis. Science 305, 217. (Pubitemid 38886729)
66. Zhang, Z.J., Schmidt, D.E., de Paulis, T., Trivedi, B.L., Onaivi, E.S., Ebert, M.H., Hewlett, W.A., 2001. Anxiolytic-like effects of DAIZAC, a selective high-affinity 5-HT(3) receptor antagonist, in the mouse elevated plus-maze. Pharmacol. Biochem. Behav. 69, 571-578. (Pubitemid 32758743)