Vortioxetine (Lu AA21004), a novel multimodal antidepressant, enhances memory in rats

Pharmacology Biochemistry and Behavior

Volumn 105, Issue , 2013, Pages 41-50

  Mørk, Arne ^a   Montezinho, Liliana P ^a   Miller, Silke ^b   Trippodi Murphy, Crista ^b   Plath, Niels ^a   Li, Yan ^b   Gulinello, Maria ^c   Sanchez, Connie ^b  

^a H LUNDBECK A S   (Denmark)

^b LUNDBECK RESEARCH USA   (United States)

^c ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

Acetylcholine; Cognitive dysfunction; Memory; Multimodal; Serotonin; Vortioxetine

Indexed keywords

ACETYLCHOLINE; HISTAMINE; LU AA 21004; UNCLASSIFIED DRUG; VORTIOXETINE;

ANIMAL EXPERIMENT; ARTICLE; BRAIN CORTEX; BRAIN LEVEL; CONDITIONING; CONTROLLED STUDY; DRUG EFFECT; HOT PLATE TEST; MALE; MEMORY; MICRODIALYSIS; NOCICEPTION; NONHUMAN; PREFRONTAL CORTEX; PRIORITY JOURNAL; RAT; RECOGNITION;

ANIMALS; ANTIDEPRESSIVE AGENTS; CONDITIONING, CLASSICAL; FEAR; MALE; MEMORY; MICRODIALYSIS; PIPERAZINES; RATS; RATS, SPRAGUE-DAWLEY; SULFIDES;

RATTUS;

EID: 84874182123     PISSN: 00913057     EISSN: 18735177     Source Type: Journal    
DOI: 10.1016/j.pbb.2013.01.019     Document Type: Article

References (99)

1. S.F. Acevedo, T. Pfankuch, H. Ohtsu, and J. Raber Anxiety and cognition in female histidine decarboxylase knockout (Hdc(-/-)) mice Behav Brain Res 168 2006 92 99 (Pubitemid 43153771)
2. A. Adell Lu-AA21004, a multimodal serotonergic agent, for the potential treatment of depression and anxiety IDrugs 13 2010 900 910
3. J.P. Aggleton, J.R. Dumont, and E.C. Warburton Unraveling the contributions of the diencephalon to recognition memory: a review Learn Mem 18 2011 384 400
4. A.D. Ait, L. Segu, S. Naili, and M.C. Buhot Serotonin 1B receptor regulation after dorsal subiculum deafferentation Brain Res Bull 38 1995 17 23
5. S. Akhondzadeh, N. Mohammadi, M. Noroozian, N. Karamghadiri, A. Ghoreishi, and A.H. Jamshidi Added ondansetron for stable schizophrenia: a double blind, placebo controlled trial Schizophr Res 107 2009 206 212
6. E. Alvarez, V. Perez, M. Dragheim, H. Loft, and F. Artigas A double-blind, randomized, placebo-controlled, active reference study of Lu AA21004 in patients with major depressive disorder Int J Neuropsychopharmacol 15 2012 589 600
7. M. Antunes, and G. Biala The novel object recognition memory: neurobiology, test procedure, and its modifications Cogn Process 13 2012 93 110
8. J. Areberg, M. Luntang-Jensen, B. Sogaard, and D.O. Nilausen Occupancy of the serotonin transporter after administration of Lu AA21004 and its relation to plasma concentration in healthy subjects Basic Clin Pharmacol Toxicol 110 2012 401 404
9. A.F. Arnsten, C.H. Lin, C.H. Van Dyck, and K.J. Stanhope The effects of 5-HT3 receptor antagonists on cognitive performance in aged monkeys Neurobiol Aging 18 1997 21 28 (Pubitemid 27062183)
10. F. Artigas, A. Adell, and P. Celada Pindolol augmentation of antidepressant response Curr Drug Targets 7 2006 139 147
11. C.R. Ashby Jr., Y. Minabe, E. Edwards, and R.Y. Wang 5-HT3-like receptors in the rat medial prefrontal cortex: an electrophysiological study Brain Res 550 1991 181 191
12. B. Bang-Andersen, T. Ruhland, M. Jorgensen, G. Smith, K. Frederiksen, and K.G. Jensen 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 2011 3206 3221
13. A. Bhardwaj, P. Wilkinson, C. Srivastava, and M. Sharma Cognitive deficits in euthymic patients with recurrent depression J Nerv Ment Dis 198 2010 513 515
14. C.M. Bird, and N. Burgess The hippocampus and memory: insights from spatial processing Nat Rev Neurosci 9 2008 182 194 (Pubitemid 351272664)
15. P.H. Boeijinga, and H.W. Boddeke Activation of 5-HT1B receptors suppresses low but not high frequency synaptic transmission in the rat subicular cortex in vitro Brain Res 721 1996 59 65
16. P. Bonaventure, M. Letavic, C. Dugovic, S. Wilson, L. Aluisio, and C. Pudiak Histamine H3 receptor antagonists: from target identification to drug leads Biochem Pharmacol 73 2007 1084 1096 (Pubitemid 46413171)
17. A. Brambilla, A. Ghiorzi, N. Pitsikas, and F. Borsini DAU 6215, a novel 5-HT3-receptor antagonist, selectively antagonizes scopolamine-induced deficit in a passive-avoidance task, but not scopolamine-induced hypermotility in rats J Pharm Pharmacol 45 1993 841 843 (Pubitemid 23272552)
18. J.D. Brioni, T.A. Esbenshade, T.R. Garrison, S.R. Bitner, and M.D. Cowart Discovery of histamine H3 antagonists for the treatment of cognitive disorders and Alzheimer's disease J Pharmacol Exp Ther 336 2011 38 46
19. M.C. Buhot Serotonin receptors in cognitive behaviors Curr Opin Neurobiol 7 1997 243 254
20. M.C. Buhot, S. Martin, and L. Segu Role of serotonin in memory impairment Ann Med 32 2000 210 221 (Pubitemid 30237566)
21. D.T. Chalmers, and S.J. Watson Comparative anatomical distribution of 5-HT1A receptor mRNA and 5-HT1A binding in rat brain - a combined in situ hybridisation/in vitro receptor autoradiographic study Brain Res 561 1991 51 60
22. A. Cipriani, C. Santilli, T.A. Furukawa, A. Signoretti, A. Nakagawa, and H. McGuire Escitalopram versus other antidepressive agents for depression Cochrane Database Syst Rev 2 2009 CD006532
23. L. Clark, S.R. Chamberlain, and B.J. Sahakian Neurocognitive mechanisms in depression: implications for treatment Annu Rev Neurosci 32 2009 57 74
24. H.F. Clarke, J.W. Dalley, H.S. Crofts, T.W. Robbins, and A.C. Roberts Cognitive inflexibility after prefrontal serotonin depletion Science 304 2004 878 880 (Pubitemid 38620188)
25. H.F. Clarke, S.C. Walker, J.W. Dalley, T.W. Robbins, and A.C. Roberts Cognitive inflexibility after prefrontal serotonin depletion is behaviorally and neurochemically specific Cereb Cortex 17 2007 18 27 (Pubitemid 44973891)
26. M. Colon-Cesario, J. Wang, X. Ramos, H.G. Garcia, J.J. Davila, and J. Laguna An inhibitor of DNA recombination blocks memory consolidation, but not reconsolidation, in context fear conditioning J Neurosci 26 2006 5524 5533 (Pubitemid 44318404)
27. S. Consolo, S. Ramponi, H. Ladinsky, and G. Baldi A critical role for D1 receptors in the 5-HT1A-mediated facilitation of in vivo acetylcholine release in rat frontal cortex Brain Res 707 1996 320 323
28. H. Dai, K. Kaneko, H. Kato, S. Fujii, Y. Jing, and A. Xu Selective cognitive dysfunction in mice lacking histamine H1 and H2 receptors Neurosci Res 57 2007 306 313 (Pubitemid 46177303)
29. A. Degroot, and M.B. Parent Increasing acetylcholine levels in the hippocampus or entorhinal cortex reverses the impairing effects of septal GABA receptor activation on spontaneous alternation Learn Mem 7 2000 293 302
30. R. Depoortere, A.L. Auclair, L. Bardin, F.C. Colpaert, B. Vacher, and A. Newman-Tancredi F15599, a preferential post-synaptic 5-HT1A receptor agonist: activity in models of cognition in comparison with reference 5-HT1A receptor agonists Eur Neuropsychopharmacol 20 2010 641 654
31. E. Dere, M.A. De Souza-Silva, B. Topic, R.E. Spieler, H.L. Haas, and J.P. Huston Histidine-decarboxylase knockout mice show deficient nonreinforced episodic object memory, improved negatively reinforced water-maze performance, and increased neo- and ventro-striatal dopamine turnover Learn Mem 10 2003 510 519 (Pubitemid 37499779)
32. M.J. Duncan, and M.R. Congleton Neural mechanisms mediating circadian phase resetting by activation of 5-HT(7) receptors in the dorsal raphe: roles of GABAergic and glutamatergic neurotransmission Brain Res 1366 2010 110 119
33. A. Ennaceur, and J. Delacour A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data Behav Brain Res 31 1988 47 59
34. T.M. Eriksson, N. Madjid, E. Elvander-Tottie, O. Stiedl, P. Svenningsson, and S.O. Ogren Blockade of 5-HT 1B receptors facilitates contextual aversive learning in mice by disinhibition of cholinergic and glutamatergic neurotransmission Neuropharmacology 54 2008 1041 1050
35. M.S. Fanselow Conditioned and unconditional components of post-shock freezing Pavlov J Biol Sci 15 1980 177 182 (Pubitemid 11190893)
36. S.H. Fatemi, E.S. Emamian, and D.A. Kist Venlafaxine and bupropion combination therapy in a case of treatment-resistant depression Ann Pharmacother 33 1999 701 703 (Pubitemid 29309729)
37. M. Fendt, and M.S. Fanselow The neuroanatomical and neurochemical basis of conditioned fear Neurosci Biobehav Rev 23 1999 743 760 (Pubitemid 29282023)
38. G. Flik, E. Dremencov, T.I. Cremers, J.H. Folgering, and B.H. Westerink The role of cortical and hypothalamic histamine-3 receptors in the modulation of central histamine neurotransmission: an in vivo electrophysiology and microdialysis study Eur J Neurosci 34 2011 1747 1755
39. D.J. Fontana, S.E. Daniels, C. Henderson, R.M. Eglen, and E.H. Wong Ondansetron improves cognitive performance in the Morris water maze spatial navigation task Psychopharmacology (Berl) 120 1995 409 417
40. I.H. Gotlib, and J. Joormann Cognition and depression: current status and future directions Annu Rev Clin Psychol 6 2010 285 312
41. E. Hajos-Korcsok, D.D. Robinson, J.H. Yu, C.S. Fitch, E. Walker, and K.M. Merchant Rapid habituation of hippocampal serotonin and norepinephrine release and anxiety-related behaviors, but not plasma corticosterone levels, to repeated footshock stress in rats Pharmacol Biochem Behav 74 2003 609 616 (Pubitemid 36126539)
42. A.A. Hancock The challenge of drug discovery of a GPCR target: analysis of preclinical pharmacology of histamine H3 antagonists/inverse agonists Biochem Pharmacol 71 2006 1103 1113 (Pubitemid 43361919)
43. L.G. Harsing Jr. The pharmacology of the neurochemical transmission in the midbrain raphe nuclei of the rat Curr Neuropharmacol 4 2006 313 339 (Pubitemid 44524467)
44. B.J. Hasselbalch, U. Knorr, and L.V. Kessing Cognitive impairment in the remitted state of unipolar depressive disorder: a systematic review J Affect Disord 134 2011 20 31
45. H. Hodges, P. Sowinski, J.J. Turner, and A. Fletcher Comparison of the effects of the 5-HT3 receptor antagonists WAY-100579 and ondansetron on spatial learning in the water maze in rats with excitotoxic lesions of the forebrain cholinergic projection system Psychopharmacology (Berl) 125 1996 146 161
46. M. Horiguchi, M. Huang, and H.Y. Meltzer The role of 5-hydroxytryptamine 7 receptors in the phencyclidine-induced novel object recognition deficit in rats J Pharmacol Exp Ther 338 2011 605 614
47. T. Horisawa, T. Ishibashi, H. Nishikawa, T. Enomoto, S. Toma, and T. Ishiyama The effects of selective antagonists of serotonin 5-HT7 and 5-HT1A receptors on MK-801-induced impairment of learning and memory in the passive avoidance and Morris water maze tests in rats: mechanistic implications for the beneficial effects of the novel atypical antipsychotic lurasidone Behav Brain Res 220 2011 83 90
48. X.J. Hu, F.H. Wang, C. Stenfors, S.O. Ogren, and J. Kehr Effects of the 5-HT1B receptor antagonist NAS-181 on extracellular levels of acetylcholine, glutamate and GABA in the frontal cortex and ventral hippocampus of awake rats: a microdialysis study Eur Neuropsychopharmacol 17 2007 580 586 (Pubitemid 47078998)
49. D.T. Hubbard, B.R. Nakashima, I. Lee, and L.K. Takahashi Activation of basolateral amygdala corticotropin-releasing factor 1 receptors modulates the consolidation of contextual fear Neuroscience 150 2007 818 828 (Pubitemid 350235791)
50. J. Izumi, M. Washizuka, N. Miura, Y. Hiraga, and Y. Ikeda Hippocampal serotonin 5-HT1A receptor enhances acetylcholine release in conscious rats J Neurochem 62 1994 1804 1808
51. C. Katona, T. Hansen, and C.K. Olsen A randomized, double-blind, placebo-controlled, duloxetine-referenced, fixed-dose study comparing the efficacy and safety of Lu AA21004 in elderly patients with major depressive disorder Int Clin Psychopharmacol 27 2012 215 223
52. G.G. Kay The effects of antihistamines on cognition and performance J Allergy Clin Immunol 105 2000 S622 S627
53. S. Khaliq, S. Haider, S.P. Ahmed, T. Perveen, and D.J. Haleem Relationship of brain tryptophan and serotonin in improving cognitive performance in rats Pak J Pharm Sci 19 2006 11 15
54. M.V. King, C.A. Marsden, and K.C. Fone A role for the 5-HT(1A), 5-HT4 and 5-HT6 receptors in learning and memory Trends Pharmacol Sci 29 2008 482 492
55. K. Kobayashi, Y. Ikeda, E. Haneda, and H. Suzuki Chronic fluoxetine bidirectionally modulates potentiating effects of serotonin on the hippocampal mossy fiber synaptic transmission J Neurosci 28 2008 6272 6280
56. C.A. Kohler, W.C. da Silva, F. Benetti, and J.S. Bonini Histaminergic mechanisms for modulation of memory systems Neural Plast 2011 2011 1 16
57. M. Lehner, A. Wislowska-Stanek, P. Maciejak, J. Szyndler, A. Sobolewska, and P. Krzascik The relationship between pain sensitivity and conditioned fear response in rats Acta Neurobiol Exp (Wars) 70 2010 56 66
58. X. Liang, V.L. Arvanov, and R.Y. Wang Inhibition of NMDA-receptor mediated response in the rat medial prefrontal cortical pyramidal cells by the 5-HT3 receptor agonist SR 57227A and 5-HT: intracellular studies Synapse 29 1998 257 268 (Pubitemid 28267935)
59. M.L. Lopez-Rodriguez, B. Benhamu, M.J. Morcillo, I. Tejada, D. Avila, and I. Marco Benzimidazole derivatives. Part 5: design and synthesis of new benzimidazole-arylpiperazine derivatives acting as mixed 5-HT1A/5-HT3 ligands Bioorg Med Chem 12 2004 5181 5191 (Pubitemid 39200619)
60. D. Marazziti, G. Consoli, M. Picchetti, M. Carlini, and L. Faravelli Cognitive impairment in major depression Eur J Pharmacol 626 2010 83 86
61. M. Matsumoto, M. Yoshioka, H. Togashi, M. Tochihara, T. Ikeda, and H. Saito Modulation of norepinephrine release by serotonergic receptors in the rat hippocampus as measured by in vivo microdialysis J Pharmacol Exp Ther 272 1995 1044 1051
62. S.L. McLean, M.L. Woolley, D. Thomas, and J.C. Neill Role of 5-HT receptor mechanisms in sub-chronic PCP-induced reversal learning deficits in the rat Psychopharmacology (Berl) 206 2009 403 414
63. M. Meeter, L. Talamini, J.A. Schmitt, and W.J. Riedel Effects of 5-HT on memory and the hippocampus: model and data Neuropsychopharmacology 31 2006 712 720
64. D. Mendelsohn, W.J. Riedel, and A. Sambeth Effects of acute tryptophan depletion on memory, attention and executive functions: a systematic review Neurosci Biobehav Rev 33 2009 926 952
65. A. Meneses Could the 5-HT1B receptor inverse agonism affect learning consolidation? Neurosci Biobehav Rev 25 2001 193 201 (Pubitemid 32366747)
66. A. Meneses Effects of the 5-HT7 receptor antagonists SB-269970 and DR 4004 in autoshaping Pavlovian/instrumental learning task Behav Brain Res 155 2004 275 282 (Pubitemid 39208910)
67. A. Meneses Do serotonin (1-7) receptors modulate short and long-term memory? Neurobiol Learn Mem 87 2007 561 572 (Pubitemid 46505109)
68. A. Meneses, and E. Hong A pharmacological analysis of serotonergic receptors: effects of their activation of blockade in learning Prog Neuropsychopharmacol Biol Psychiatry 21 1997 273 296 (Pubitemid 27149392)
69. A. Meneses, and E. Hong 5-HT1A receptors modulate the consolidation of learning in normal and cognitively impaired rats Neurobiol Learn Mem 71 1999 207 218 (Pubitemid 29397969)
70. J.M. Miwa, R. Freedman, and H.A. Lester Neural systems governed by nicotinic acetylcholine receptors: emerging hypotheses Neuron 70 2011 20 33
71. B. Mlinar, C. Falsini, and R. Corradetti Pharmacological characterization of 5-HT(1B) receptor-mediated inhibition of local excitatory synaptic transmission in the CA1 region of rat hippocampus Br J Pharmacol 138 2003 71 80 (Pubitemid 36194205)
72. L.P. Montezinho, S. Miller, N. Plath, N.H. Jensen, J.J. Karlsson, and L. Witten The effects of acute treatment with escitalopram on the different stages of contextual fear conditioning are reversed by atomoxetine Psychopharmacology (Berl) 212 2010 131 143
73. S. Montgomery, T. Hansen, and S. Kasper Efficacy of escitalopram compared to citalopram: a meta-analysis Int J Neuropsychopharmacol 14 2011 261 268
74. A. Mørk, A. Pehrson, B.L. Tottrup, N.S. Moller, H. Zhong, and A.B. Lassen Pharmacological effects of Lu AA21004: a novel multimodal compound for the treatment of major depressive disorder J Pharmacol Exp Ther 340 2012 666 675
75. S.L. Naismith, W.A. Longley, E.M. Scott, and I.B. Hickie Disability in major depression related to self-rated and objectively-measured cognitive deficits: a preliminary study BMC Psychiatry 7 2007 32 38
76. J.C. Nelson, and G.I. Papakostas Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis of placebo-controlled randomized trials Am J Psychiatry 166 2009 980 991
77. A. Newman-Tancredi, J.C. Martel, M.B. Assie, J. Buritova, E. Lauressergues, and C. Cosi Signal transduction and functional selectivity of F15599, a preferential post-synaptic 5-HT1A receptor agonist Br J Pharmacol 156 2009 338 353
78. A. Nikiforuk Selective blockade of 5-HT7 receptors facilitates attentional set-shifting in stressed and control rats Behav Brain Res 226 2012 118 123
79. S.O. Ogren, T.M. Eriksson, E. Elvander-Tottie, C. D'Addario, J.C. Ekstrom, and P. Svenningsson The role of 5-HT(1A) receptors in learning and memory Behav Brain Res 195 2008 54 77
80. B. Olivier, and R van. Oorschot 5-HT1B receptors and aggression: a review Eur J Pharmacol 526 2005 207 217
81. A. Pazos, and J.M. Palacios Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors Brain Res 346 1985 205 230 (Pubitemid 16241111)
82. A.L. Pehrson, T. Cremers, C. Betry, M.G. Van Der Hart, L. Jorgensen, M. Madsen, N. Haddjeri, B. Ebert, and C. Sanchez Lu AA21004, a novel multimodal antidepressant, produces regionally selective increases of multiple neurotransmitters - a rat microdialysis and electrophysiology study Eur Neuropsychopharmacol 23 2013 133 145
83. G. Pepeu, and M.G. Giovannini Cholinesterase inhibitors and beyond Curr Alzheimer Res 6 2009 86 96
84. N. Pitsikas, and F. Borsini Itasetron (DAU 6215) prevents age-related memory deficits in the rat in a multiple choice avoidance task Eur J Pharmacol 311 1996 115 119 (Pubitemid 26330365)
85. A.M. Polter, and X. Li 5-HT1A receptor-regulated signal transduction pathways in brain Cell Signal 22 2010 1406 1412
86. B. Ravnkilde, P. Videbech, K. Clemmensen, A. Egander, N.A. Rasmussen, and R. Rosenberg Cognitive deficits in major depression Scand J Psychol 43 2002 239 251
87. W.J. Riedel, T. Klaassen, and J.A. Schmitt Tryptophan, mood, and cognitive function Brain Behav Immun 16 2002 581 589 (Pubitemid 35333738)
88. F.S. Roman, and E. Marchetti Involvement of 5-HT receptors in learning and memory IDrugs 1 1998 109 121 (Pubitemid 128754053)
89. M. Roychoudhury, and S.K. Kulkarni Effects of ondansetron on short-term memory retrieval in mice Methods Find Exp Clin Pharmacol 19 1997 43 46 (Pubitemid 27167763)
90. A.J. Rush, M.H. Trivedi, S.R. Wisniewski, A.A. Nierenberg, J.W. Stewart, and D. Warden Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report Am J Psychiatry 163 2006 1905 1917 (Pubitemid 44807782)
91. A. Sambeth, A. Blokland, C.J. Harmer, T.O. Kilkens, P.J. Nathan, and R.J. Porter Sex differences in the effect of acute tryptophan depletion on declarative episodic memory: a pooled analysis of nine studies Neurosci Biobehav Rev 31 2007 516 529 (Pubitemid 46546436)
92. C. Sanchez, A. Pehrson, T. Cremers, L.P. Montezinho, C. Trippodi-Murphy, and Y. Li Lu AA21004, a multimodal antidepressant, is active in a fluoxetine-insensitive rat model of depression and enhances cognitive function in rats American Psychiatric Association, 165th Annual Meeting, May 5-9, 2012, Philadelphia, PA 2012
93. L.M. Savage Sustaining high acetylcholine levels in the frontal cortex, but not retrosplenial cortex, recovers spatial memory performance in a rodent model of diencephalic amnesia Behav Neurosci 126 2012 226 236
94. T.L. Wallace, T.M. Ballard, B. Pouzet, W.J. Riedel, and J.G. Wettstein Drug targets for cognitive enhancement in neuropsychiatric disorders Pharmacol Biochem Behav 99 2011 130 145
95. K.A. Waters, T.O. Stean, B. Hammond, D.J. Virley, N. Upton, and J.N. Kew Effects of the selective 5-HT(7) receptor antagonist SB-269970 in animal models of psychosis and cognition Behav Brain Res 228 2012 211 218
96. L. Westrich, A. Pehrson, H. Zhong, S.M. Nielsen, K. Frederiksen, and T.B. Stensbøl In vitro and in vivo effects of the multimodal antidepressant vortioxetine (Lu AA21004) at human and rat targets Int J Psychiatry Clin Pract 5 Suppl. 1 2012 47
97. M. Wijtmans, R. Leurs, and I. De Esch Histamine H3 receptor ligands break ground in a remarkable plethora of therapeutic areas Expert Opin Investig Drugs 16 2007 967 985 (Pubitemid 47074155)
98. Z. Yan Regulation of GABAergic inhibition by serotonin signaling in prefrontal cortex: molecular mechanisms and functional implications Mol Neurobiol 26 2002 203 216 (Pubitemid 35239800)
99. H. Zhong, N. Haddjeri, and C. Sanchez Escitalopram, an antidepressant with an allosteric effect at the serotonin transporter - a review of current understanding of its mechanism of action Psychopharmacology (Berl) 219 2012 1 13