Atomoxetine affects transcription/translation of the NMDA receptor and the norepinephrine transporter in the rat brain - an in vivo study

Drug Design, Development and Therapy

Volumn 7, Issue , 2013, Pages 1433-1446

  Udvardi, Patrick T ^a   Föhr, Karl J ^a   Henes, Carolin ^a   Liebau, Stefan ^a   Dreyhaupt, Jens ^a   Boeckers, Tobias M ^a   Ludolph, Andrea G ^a  

^a UNIVERSITY OF ULM   (Germany)

Author keywords

Altered gene expression; Atomoxetine; Attention deficit hyperactivity disorder (ADHD); In vivo study; N methyl D aspartate receptor; Neurodevelopment

Indexed keywords

ATOMOXETINE; MESSENGER RNA; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; N METHYL DEXTRO ASPARTIC ACID RECEPTOR 2B; NORADRENALIN TRANSPORTER; SNARE PROTEIN; SODIUM CHLORIDE; SYNAPTOPHYSIN; SYNAPTOSOMAL ASSOCIATED PROTEIN 25;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; CORPUS STRIATUM; DRUG EFFECT; DRUG MECHANISM; GLUTAMATERGIC TRANSMISSION; HIPPOCAMPUS; IN VIVO STUDY; MALE; MESENCEPHALON; NEUROTRANSMISSION; NONHUMAN; PREFRONTAL CORTEX; PROTEIN ANALYSIS; PROTEIN LOCALIZATION; RAT; RNA ANALYSIS; RNA TRANSCRIPTION; RNA TRANSLATION; SYNAPSE; TREATMENT DURATION;

ALTERED GENE EXPRESSION; ATOMOXETINE; ATTENTION-DEFICIT HYPERACTIVITY DISORDER (ADHD); IN VIVO STUDY; N-METHYL-D-ASPARTATE RECEPTOR; NEURODEVELOPMENT;

ADRENERGIC UPTAKE INHIBITORS; ANIMALS; ATTENTION DEFICIT DISORDER WITH HYPERACTIVITY; BRAIN; GENE EXPRESSION REGULATION; GLUTAMIC ACID; INJECTIONS, INTRAPERITONEAL; MALE; NOREPINEPHRINE PLASMA MEMBRANE TRANSPORT PROTEINS; PROPYLAMINES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, N-METHYL-D-ASPARTATE; RNA, MESSENGER; SPECIES SPECIFICITY; TIME FACTORS; TRANSCRIPTION, GENETIC;

EID: 84889652757     PISSN: 11778881     EISSN: None     Source Type: Journal    
DOI: 10.2147/DDDT.S50448     Document Type: Article

References (80)

1. Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA. The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry. 2007; 164(6): 942-948.
2. Biederman J, Faraone SV. Attention-deficit hyperactivity disorder. Lancet. 2005; 366(9481): 237-248.
3. Spencer TJ, Biederman J, Mick E. Attention-deficit/hyperactivity disorder: diagnosis, lifespan, comorbidities, and neurobiology. J Pediatr Psychol. 2007; 32(6): 631-642.
4. Kessler RC, Adler L, Barkley R, et al. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry. 2006; 163(4): 716-723.
5. Stahl S. Attention deficit hyperactivity disorder and its treatmented. In: Stahl S, editor. Stahl's Essential Psychopharmacocogy. 3rd ed. New York, NY: Cambridge University Press; 2008: 863-897.
6. Gibson AP, Bettinger TL, Patel NC, Crismon ML. Atomoxetine versus stimulants for treatment of attention deficit/hyperactivity disorder. Ann Pharmacother. 2006; 40(6): 1134-1142.
7. Molina BS, Hinshaw SP, Swanson JM, et al; MTA Cooperative Group. The MTA at 8 years: prospective follow-up of children treated for combined-type ADHD in a multisite study. J Am Acad Child Adolesc Psychiatry. 2009; 48(5): 484-500.
8. Ferris RM, Tang FL, Maxwell RA. A comparison of the capacities of isomers of amphetamine, deoxypipradrol and methylphenidate to inhibit the uptake of tritiated catecholamines into rat cerebral cortex slices, synaptosomal preparations of rat cerebral cortex, hypothalamus and striatum and into adrenergic nerves of rabbit aorta. J Pharmacol Exp Ther. 1972; 181(3): 407-416.
9. Schweri MM, Skolnick P, Rafferty MF, Rice KC, Janowsky AJ, Paul SM. [3H]Threo-(P/-)-methylphenidate binding to 3, 4-dihydroxyphenylethylamine uptake sites in corpus striatum: correlation with the stimulant properties of ritalinic acid esters. J Neurochem. 1985; 45(4): 1062-1070.
10. Carrey NJ, MacMaster FP, Gaudet L, Schmidt MH. Striatal creatine and glutamate/glutamine in attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2007; 17(1): 11-17.
11. Lule D, Ludolph AC, Ludolph AG. Neurodevelopmental and neurodegenerative diseases-is there a pathophysiological link? Attention-deficit/hyperactivity disorder and amyotrophic lateral sclerosis as examples. Med Hypotheses. 2008; 70(6): 1133-1138.
12. Orrego F, Villanueva S. The chemical nature of the main central excitatory transmitter: a critical appraisal based upon release studies and synaptic vesicle localization. Neuroscience. 1993; 56(3): 539-555.
13. Davies J, Evans RH, Francis AA, Watkins JC. Excitatory amino acid receptors and synaptic excitation in the mammalian central nervous system. J Physiol (Paris). 1979; 75(6): 641-654.
14. Cull-Candy S, Brickley S, Farrant M. NMDA receptor subunits: diversity, development and disease. Curr Opin Neurobiol. 2001; 11(3): 327-335.
15. Köhr G, Jensen V, Koester HJ, et al. Intracellular domains of NMDA receptor subtypes are determinants for long-term potentiation induction. J Neurosci. 2003; 23(34): 10791-10799.
16. Monyer H, Burnashev N, Laurie DJ, Sakmann B, Seeburg PH. Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron. 1994; 12(3): 529-540.
17. Stocca G, Vicini S. Increased contribution of NR2A subunit to synaptic NMDA receptors in developing rat cortical neurons. J Physiol. 1998; 507(Pt 1): 13-24.
18. Tovar KR, Westbrook GL. The incorporation of NMDA receptors with a distinct subunit composition at nascent hippocampal synapses in vitro. J Neurosci. 1999; 19(10): 4180-4188.
19. Li B, Chen N, Luo T, Otsu Y, Murphy TH, Raymond LA. Differential regulation of synaptic and extra-synaptic NMDA receptors. Nat Neurosci. 2002; 5(9): 833-834.
20. Köhr G. NMDA receptor function: subunit composition versus spatial distribution. Cell Tissue Res. 2006; 326(2): 439-446.
21. Hardingham GE, Fukunaga Y, Bading H. Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways. Nat Neurosci. 2002; 5(5): 405-414.
22. Jensen V, Rinholm JE, Johansen TJ, et al. N-methyl-D-aspartate receptor subunit dysfunction at hippocampal glutamatergic synapses in an animal model of attention-deficit/hyperactivity disorder. Neuroscience. 2009; 158(1): 353-364.
23. Malinow R, Malenka RC. AMPA receptor trafficking and synaptic plasticity. Annu Review Neurosci. 2002; 25: 103-126.
24. Bredt DS, Nicoll RA. AMPA receptor trafficking at excitatory synapses. Neuron. 2003; 40(2): 361-379.
25. Lou HC. Etiology and pathogenesis of attention-deficit hyperactivity disorder (ADHD): significance of prematurity and perinatal hypoxic-haemodynamic encephalopathy. Acta Paediatr. 1996; 85(11): 1266-1271.
26. Gehlert DR, Schober DA, Gackenheimer SL. Comparison of (R)-[3H]tomoxetine and (R/S)-[3H]nisoxetine binding in rat brain. J Neurochem. 1995; 64(6): 2792-2800.
27. Bymaster FP, Katner JS, Nelson DL, et al. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology. 2002; 27(5): 699-711.
28. Easton N, Steward C, Marshall F, Fone K, Marsden C. Effects of amphetamine isomers, methylphenidate and atomoxetine on synaptosomal and synaptic vesicle accumulation and release of dopamine and noradrenaline in vitro in the rat brain. Neuropharmacology. 2007; 52(2): 405-414.
29. Peterson K, McDonagh MS, Fu R. Comparative benefits and harms of competing medications for adults with attention-deficit hyperactivity disorder: a systematic review and indirect comparison meta-analysis. Psychopharmacology (Berl). 2008; 197(1): 1-11.
30. Seneca N, Gulyás B, Varrone A, et al. Atomoxetine occupies the norepinephrine transporter in a dose-dependent fashion: a PET study in nonhuman primate brain using (S, S)-[18F]FMeNER-D2. Psychopharmacology (Berl). 2006; 188(1): 119-127.
31. Takano A, Gulyás B, Varrone A, Maguire RP, Halldin C. Saturated norepinephrine transporter occupancy by atomoxetine relevant to clinical doses: a rhesus monkey study with (S, S)-[(18)F]FMeNER-D (2). Eur J Nucl Med Mol Imaging. 2009; 36(8): 1308-1314.
32. Kratochvil CJ, Heiligenstein JH, Dittmann R, et al. Atomoxetine and methylphenidate treatment in children with ADHD: a prospective, randomized, open-label trial. J Am Acad Child Adolesc Psychiatry. 2002; 41(7): 776-784.
33. Hiemke C, Baumann P, Bergemann N, et al. AGNP consensus guidelines for therapeutic drug monitoring in psychiatry: update 2011. Pharmacopsychiatry. 2011; 44(6): 195-235.
34. Kielbasa W, Kalvass JC, Stratford R. Microdialysis evaluation of atomoxetine brain penetration and central nervous system pharmacokinetics in rats. Drug Metab Dispos. 2009; 37(1): 137-142.
35. Scherer D, Hassel D, Bloehs R, et al. Selective noradrenaline reuptake inhibitor atomoxetine directly blocks hERG currents. Br J Pharmacol. 2009; 156(2): 226-236.
36. Ludolph AG, Udvardi PT, Schaz U, et al. Atomoxetine acts as an NMDA receptor blocker in clinically relevant concentrations. Br J Pharmacol. 2010; 160(2): 283-291.
37. Lempp T, Toennes SW, Wunder C, et al. Altered gene expression in the prefrontal cortex of young rats induced by the ADHD drug atomoxetine. Prog Neuropsychopharmacol Biol Psychiatry. 2013; 40: 221-228.
38. Ikonomidou C, Bittigau P, Koch C, et al. Neurotransmitters and apoptosis in the developing brain. Biochem Pharmacol. 2001; 62(4): 401-405.
39. Paxinos G, Watson C. The Rat Brain: In Stereotactic Coordinates. 2nd Ed. London: Academic Press; 1986.
40. Vandesompele J, De Preter K, Pattyn F, et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome biology. RESEARCH0034. 2002; 3(7).
41. Mestdagh P, Van Vlierberghe P, De Weer A, et al. A novel and universal method for microRNA RT-qPCR data normalization. Genome biology. 2009; 10(6): R64.
42. Schaffner W, Weissmann C. A rapid, sensitive, and specific method for the determination of protein in dilute solution. Anal Biochem. 1973; 56(2): 502-514.
43. Aldridge GM, Podrebarac DM, Greenough WT, Weiler IJ. The use of total protein stains as loading controls: an alternative to high-abundance single-protein controls in semi-quantitative immunoblotting. J Neurosci Methods. 2008; 172(2): 250-254.
44. Bayles R, Harikrishnan KN, Lambert E, et al. Epigenetic modification of the norepinephrine transporter gene in postural tachycardia syndrome. Arterioscler Thromb Vasc Biol. 2012; 32(8): 1910-1916.
45. Altafaj X, Ortiz-Abalia J, Fernández M, et al. Increased NR2A expression and prolonged decay of NMDA-induced calcium transient in cerebellum of TgDyrk1A mice, a mouse model of Down syndrome. Neurobiol Dis. 2008; 32(3): 377-384.
46. Uriu Y, Kiyonaka S, Miki T, et al. Rab3-interacting molecule gamma isoforms lacking the Rab3-binding domain induce long lasting currents but block neurotransmitter vesicle anchoring in voltage-dependent P/Q-type Ca2oochannels. J Biol Chem. 2010; 285(28): 21750-21767.
47. Chalazonitis A, Tang AA, Shang Y, et al. Homeodomain interacting protein kinase 2 regulates postnatal development of enteric dopaminergic neurons and glia via BMP signaling. J Neurosci. 2011; 31(39): 13746-13757.
48. Michelson D, Faries D, Wernicke J, et al; Atomoxetine ADHD Study Group. Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, dose-response study. Pediatrics. 2001; 108(5): E83.
49. Gehlert DR, Gackenheimer SL, Robertson DW. Localization of rat brain binding sites for [3H]tomoxetine, an enantiomerically pure ligand for norepinephrine reuptake sites. Neurosci Lett. 1993; 157(2): 203-206.
50. Arcos-Burgos M, Londoño AC, Pineda DA, et al. Analysis of brain metabolism by proton magnetic resonance spectroscopy (1H-MRS) in attention-deficit/hyperactivity disorder suggests a generalized differential ontogenic pattern from controls. Atten Defic Hyperact Disord. 2012; 4(4): 205-212.
51. Wiguna T, Guerrero APS, Wibisono S, Sastroasmoro S. Effect of 12-week administration of 20-mg long-acting methylphenidate on Glu/Cr, NAA/Cr, Cho/Cr, and mI/Cr ratios in the prefrontal cortices of school-age children in Indonesia: a study using 1H magnetic resonance spectroscopy (MRS). Clin Neuropharmacol. 2012; 35(2): 81-85.
52. Carrey N, MacMaster FP, Fogel J, et al. Metabolite changes resulting from treatment in children with ADHD: a 1H-MRS study. Clin Neuropharmacol. 2003; 26(4): 218-221.
53. Tafazoli S, O'Neill J, Bejjani A, et al. 1H MRSI of middle frontal gyrus in pediatric ADHD. J Psychiatr Res. 2013; 47(4): 505-512.
54. Duguid IC, Smart TG. Presynaptic NMDAR receptors. In: VanDongen AM, editor. Biology of the NMDAR Receptor. Boca Raton, FL: CRC Press; 2009: 313-328.
55. Langer SZ. Presynaptic autoreceptors regulating transmitter release. Neurochem Int. 2008; 52(1-2): 26-30.
56. Stevens CF. Presynaptic function. Curr Opin Neurobiol. 2004; 14(3): 341-345.
57. Sudhof TC. The synaptic vesicle cycle. Annu Rev Neurosci. 2004; 27: 509-547.
58. Pittaluga A, Raiteri M. N-methyl-D-aspartic acid (NMDA) and non-NMDA receptors regulating hippocampal norepinephrine release. III. Changes in the NMDA receptor complex induced by their functional cooperation. J Pharmacol Exp Ther. 1992; 263(1): 327-333.
59. Rammes G, Mahal B, Putzke J, et al. The anti-craving compound acamprosate acts as a weak NMDA-receptor antagonist, but modulates NMDA-receptor subunit expression similar to memantine and MK-801. Neuropharmacology. 2001; 40(6): 749-760.
60. Sheng M, Cummings J, Roldan LA, Jan YN, Jan LY. Changing subunit composition of heteromeric NMDA receptors during development of rat cortex. Nature. 1994; 368(6467): 144-147.
61. Wenzel A, Fritschy JM, Mohler H, Benke D. NMDA receptor heterogeneity during postnatal development of the rat brain: differential expression of the NR2A, NR2B, and NR2C subunit proteins. J Neurochem. 1997; 68(2): 469-478.
62. Barria A, Malinow R. NMDA receptor subunit composition controls synaptic plasticity by regulating binding to CaMKII. Neuron. 2005; 48(2): 289-301.
63. Martin D, Bustos GA, Bowe MA, Bray SD, Nadler JV. Autoreceptor regulation of glutamate and aspartate release from slices of the hippocampal CA1 area. J Neurochem. 1991; 56(5): 1647-1655.
64. Paoletti P, Neyton J. NMDA receptor subunits: function and pharmacology. Curr Opin Pharmacol. 2007; 7(1): 39-47.
65. Guo Y, Xiao P, Lei S, et al. How is mRNA expression predictive for protein expression? A correlation study on human circulating monocytes. Acta Biochim Biophys Sin (Shanghai). 2008; 40(5): 426-436.
66. MacMaster FP, Carrey N, Sparkes S, Kusumakar V. Proton spectroscopy in medication-free pediatric attention-deficit/hyperactivity disorder. Biol Psychiatry. 2003; 53(2): 184-187.
67. Ikonomidou C, Bosch F, Miksa M, et al. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science. 1999; 283(5398): 70-74.
68. Findling RL, Short EJ, McNamara NK, et al. Methylphenidate in the treatment of children and adolescents with bipolar disorder and attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2007; 46(11): 1445-1453.
69. Standaert DG, Testa CM, Young AB, Penney JB. Organization of N-methyl-D-aspartate glutamate receptor gene expression in the basal ganglia of the rat. J Comp Neurol. 1994; 343(1): 1-16.
70. Puliti A, Rossi PI, Caridi G, et al. Albuminuria and glomerular damage in mice lacking the metabotropic glutamate receptor 1. Am J Pathol. 2011; 178(3): 1257-1269.
71. Neale BM, Lasky-Su J, Anney R, et al. Genome-wide association scan of attention deficit hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet. 2008; 147B(8): 1337-1344.
72. Lesch KP, Timmesfeld N, Renner TJ, et al. Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies. J Neural Transm. 2008; 115(11): 1573-1585.
73. Romanos M, Freitag C, Jacob C, et al. Genome-wide linkage analysis of ADHD using high-density SNP arrays: novel loci at 5q13. 1 and 14q12. Mol Psychiatry. 2008; 13(5): 522-530.
74. Franke B, Neale BM, Faraone SV. Genome-wide association studies in ADHD. Hum Genet. 2009; 126(1): 13-50.
75. Poelmans G, Pauls DL, Buitelaar JK, Franke B. Integrated genome-wide association study findings: identification of a neurodevelopmental network for attention deficit hyperactivity disorder. Am J Psychiatry. 2011; 168(4): 365-377.
76. Ramocki MB, Zoghbi HY. Failure of neuronal homeostasis results in common neuropsychiatric phenotypes. Nature. 2008; 455(7215): 912-918.
77. Hess EJ, Jinnah HA, Kozak CA, Wilson MC. Spontaneous locomotor hyperactivity in a mouse mutant with a deletion including the Snap gene on chromosome 2. J Neurosci. 1992; 12(7): 2865-2874.
78. Hess EJ, Collins KA, Wilson MC. Mouse model of hyperkinesis implicates SNAP-25 in behavioral regulation. J Neurosci. 1996; 16(9): 3104-3111.
79. Sagvolden T. Behavioral validation of the spontaneously hypertensive rat (SHR) as an animal model of attention-deficit/hyperactivity disorder (AD/HD). Neurosci Biobehav Rev. 2000; 24(1): 31-39.
80. Sagvolden T, Johansen EB, Aase H, Russell VA. A dynamic developmental theory of attention-deficit/hyperactivity disorder (ADHD) predominantly hyperactive/impulsive and combined subtypes. Behav Brain Sci. 2005; 28(3): 397-419; discussion 419-468.