Antidepressant-Like Effects of CX717, a Positive Allosteric Modulator of AMPA Receptors.
Ampakine
Antidepressant
BDNF
Prefrontal cortex
p11
Journal
Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
12
03
2020
accepted:
26
05
2020
pubmed:
15
6
2020
medline:
8
6
2021
entrez:
15
6
2020
Statut:
ppublish
Résumé
Conventional antidepressant drugs elevate the availability of monoamine neurotransmitters. However, these pharmacological therapies have limited efficacy and a slow onset of action as main limitations. New glutamatergic drugs such as ketamine have shown promise as a rapid-acting antidepressant drugs although with adverse effects. The mechanism of action of ketamine is hypothesized to involve a dis-inhibition of cortical pyramidal neurons produced by an stimulation of AMPA receptors by glutamate. In this context, low-impact positive allosteric modulators of the AMPA receptors (a.k.a. ampakines) have been regarded as potential antidepressant drugs. Here, we have examined the behavioral, biochemical, and molecular effects of a low-impact ampakine, CX717. Our results show that CX717 has a rapid (30 min) but short-lasting (up to 24 h) antidepressant-like effect in the forced swim test. Intra-cortical infusion of CX717 increases the efflux of noradrenaline, dopamine, and serotonin, but not glutamate. However, systemic CX717 does not alter these neurotransmitters. CX717 also produced a rapid (up to 1 h) increase of brain-derived neurotrophic factor (BDNF) and a more sustained (up to 6 h) increase of p11. Overall, CX717 appears to possess a rapid but not sustained antidepressant action possibly caused by rapid increases of BDNF and p11.
Identifiants
pubmed: 32535760
doi: 10.1007/s12035-020-01954-x
pii: 10.1007/s12035-020-01954-x
doi:
Substances chimiques
Antidepressive Agents
0
Brain-Derived Neurotrophic Factor
0
CX717
0
Cell-Penetrating Peptides
0
Isoxazoles
0
Receptors, AMPA
0
p11 peptide
0
Serotonin
333DO1RDJY
Glutamic Acid
3KX376GY7L
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3498-3507Subventions
Organisme : Instituto de Salud Carlos III
ID : FIS Grant PI16/00217
Références
Dingledine R, Borges K, Bowie D, Traynelis SF (1999) The glutamate receptor ion channels. Pharmacol Rev 51:7–61
pubmed: 10049997
Beneyto M, Kristiansen LV, Oni-Orisan A, McCullumsmith RE, Meador-Woodruff JH (2007) Abnormal glutamate receptor expression in the medial temporal lobe in schizophrenia and mood disorders. Neuropsychopharmacology 32:1888–1902
pubmed: 17299517
Duric V, Banasr M, Stockmeier CA, Simen AA, Newton SS, Overholser JC, Jurjus GJ, Dieter L et al (2013) Altered expression of synapse and glutamate related genes in post-mortem hippocampus of depressed subjects. Int J Neuropsychopharmacol 16:69–82
pubmed: 22339950
Wisden W, Seeburg PH, Monyer H (2000) AMPA, kainate and NMDA ionotropic glutamate receptor expression – an in situ hybridization atlas. In: Ottersen OP, Storm-Mathisen J (eds) Handbook of Chemical Neuroanatomy, Glutamate, vol 18. Elsevier, Amsterdam, pp. 99–143
Beneyto M, Meador-Woodruff JH (2008) Lamina-specific abnormalities of NMDA receptor-associated postsynaptic protein transcripts in the prefrontal cortex in schizophrenia and bipolar disorder. Neuropsychopharmacology 33:2175–2186
pubmed: 18033238
Barbon A, Caracciolo L, Orlandi C, Musazzi L, Mallei A, La Via L, Bonini D, Mora C et al (2011) Chronic antidepressant treatments induce a time-dependent up-regulation of AMPA receptor subunit protein levels. Neurochem Int 59:896–905
pubmed: 21839792
Akinfiresoye L, Tizabi Y (2013) Antidepressant effects of AMPA and ketamine combination: role of hippocampal BDNF, synapsin, and mTOR. Psychopharmacology 230:291–298
pubmed: 23732839
Jiménez-Sánchez L, Castañé A, Pérez-Caballero L, Grifoll-Escoda M, López-Gil X, Campa L, Galofré M, Berrocoso E et al (2016) Activation of AMPA receptors mediates the antidepressant action of deep brain stimulation of the infralimbic prefrontal cortex. Cereb Cortex 26:2778–2789
pubmed: 26088969
Maeng S, Zarate CA Jr, Du J, Schloesser RJ, McCammon J, Chen G, Manji HK (2008) Cellular mechanisms underlying the antidepressant effects of ketamine: Role of a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biol Psychiatry 63:349–352
pubmed: 17643398
Autry AE, Adachi M, Nosyreva E, Na ES, Los MF, Cheng PF, Kavalali ET, Monteggia LM (2011) NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature 475:91–95
pubmed: 21677641
pmcid: 3172695
Koike H, Iijima M, Chaki S (2011) Involvement of AMPA receptor in both the rapid and sustained antidepressant-like effects of ketamine in animal models of depression. Behav Brain Res 224:107–111
pubmed: 21669235
Melendez RI, Kalivas PW (2003) Metabotropic glutamate receptor regulation of extracellular glutamate levels in the prefrontal cortex. Ann NY Acad. Sci 1003:443–444
pubmed: 14684483
Xi ZX, Baker DA, Shen H, Carson DS, Kalivas PW (2002) Group II metabotropic glutamate receptors modulate extracellular glutamate in the nucleus accumbens. J Pharmacol Exp Ther 300:162–171
pubmed: 11752112
Karasawa J, Shimazaki T, Kawashima N, Chaki S (2005) AMPA receptor stimulation mediates the antidepressant-like effect of a group II metabotropic glutamate receptor antagonist. Brain Res 1042:92–98
pubmed: 15823257
Witkin JM, Monn JA, Schoepp DD, Li X, Overshiner C, Mitchell SN, Carter G, Johnson B et al (2016) The rapidly acting antidepressant ketamine and the mGlu2/3 receptor antagonist LY341495 rapidly engage dopaminergic mood circuits. J Pharmacol Exp Ther 358:71–82
pubmed: 27189960
Derkach VA, Oh MC, Guire ES, Soderling TR (2007) Regulatory mechanisms of AMPA receptors in synaptic plasticity. Nat Rev Neurosci 8:101–113
pubmed: 17237803
O'Neill MJ, Dix S (2007) AMPA receptor potentiators as cognitive enhancers. IDrugs 10:185–192
pubmed: 17351873
Hampson RE, España RA, Rogers GA, Porrino LJ, Deadwyler SA (2009) Mechanisms underlying cognitive enhancement and reversal of cognitive deficits in nonhuman primates by the ampakine CX717. Psychopharmacology 202:355–369
pubmed: 18985324
Kunugi A, Tanaka M, Suzuki A, Tajima Y, Suzuki N, Suzuki M, Nakamura S, Kuno H et al (2019) TAK-137, an AMPA-R potentiator with little agonistic effect, has a wide therapeutic window. Neuropsychopharmacology 44:961–970
pubmed: 30209408
Meldrum BS (1994) The role of glutamate in epilepsy and other CNS disorders. Neurology 44(Suppl 8):S14–S23
pubmed: 7970002
Lynch G (2006) Glutamate-based therapeutic approaches: ampakines. Curr Opin Pharmacol 6:82–88
pubmed: 16361116
Lapidus KA, Soleimani L, Murrough JW (2013) Novel glutamatergic drugs for the treatment of mood disorders. Neuropsychiatr Dis Treat 9:1101–1112
pubmed: 23976856
pmcid: 3747027
Arai A, Guidotti A, Costa E, Lynch G (1996) Effect of the AMPA receptor modulator IDRA 21 on LTP in hippocampal slices. Neuroreport 7:2211–2215
pubmed: 8930991
Li X, Tizzano JP, Griffey K, Clay M, Lindstrom T, Skolnick P (2001) Antidepressant-like actions of an AMPA receptor potentiator (LY392098). Neuropharmacology 40:1028–1033
pubmed: 11406194
Knapp RJ, Goldenberg R, Shuck C, Cecil A, Watkins J, Miller C, Crites G, Malatynska E (2002) Antidepressant activity of memory-enhancing drugs in the reduction of submissive behavior model. Eur J Pharmacol 440:27–35
pubmed: 11959085
Alt A, Nisenbaum ES, Bleakman D, Witkin JM (2006) A role for AMPA receptors in mood disorders. Biochem Pharmacol 71:1273–1288
pubmed: 16442080
Boyle J, Stanley N, James LM, Wright N, Johnsen S, Arbon EL, Dijk DJ (2012) Acute sleep deprivation: the effects of the AMPAKINE compound CX717 on human cognitive performance, alertness and recovery sleep. J Psychopharmacol 26:1047–1057
pubmed: 21940760
Oertel BG, Felden L, Tran PV, Bradshaw MH, Angst MS, Schmidt H, Johnson S, Greer JJ et al (2010) Selective antagonism of opioid-induced ventilatory depression by an ampakine molecule in humans without loss of opioid analgesia. Clin Pharmacol Ther 87:204–211
pubmed: 19907420
Wesensten NJ, Reichardt RM, Balkin TJ (2007) Ampakine (CX717) effects on performance and alertness during simulated night shift work. Aviat Space Environ Med 78:937–943
pubmed: 17955941
Porrino LJ, Daunais JB, Rogers GA, Hampson RE, Deadwyler SA (2005) Facilitation of task performance and removal of the effects of sleep deprivation by an ampakine (CX717) in nonhuman primates. PLoS Biol 3:e299
pubmed: 16104830
pmcid: 1188239
Andreasen JT, Gynther M, Rygaard A, Bøgelund T, Nielsen SD, Clausen RP, Mogensen J, Pickering DS (2013) Does increasing the ratio of AMPA-to-NMDA receptor mediated neurotransmission engender antidepressant action? Studies in the mouse forced swim and tail suspension tests. Neurosci Lett 546:6–10
pubmed: 23643996
Li X, Witkin JM, Need AB, Skolnick P (2003) Enhancement of antidepressant potency by a potentiator of AMPA receptors. Cell Mol Neurobiol 23:419–430
pubmed: 12825836
Ren J, Lenal F, Yang M, Ding X, Greer JJ (2013) Coadministration of the AMPAKINE CX717 with propofol reduces respiratory depression and fatal apneas. Anesthesiology 118:1437–1445
pubmed: 23542802
Ren J, Ding X, Greer JJ (2012) Respiratory depression in rats induced by alcohol and barbiturate and rescue by ampakine CX717. J Appl Physiol 113:1004–1011
pubmed: 22837171
pmcid: 3487499
Cryan JF, Valentino RJ, Lucki I (2005) Assessing substrates underlying the behavioral effects of antidepressants using the modi?ed rat forced swimming test. Neurosci Biobehav Rev 29:547–569
pubmed: 15893822
Benveniste H, Diemer NH (1987) Cellular reactions to implantation of a microdialysis tube in the rat hippocampus. Acta Neuropathol 74:234–238
pubmed: 3673515
Benveniste H, Drejer J, Schousboe A, Diemer NH (1987) Regional cerebral glucose phosphorylation and blood flow after insertion of a microdialysis fiber through the dorsal hippocampus in the rat. J Neurochem 49:729–734
pubmed: 3612121
Detke MJ, Rickels M, Lucki I (1995) Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants. Psychopharmacology 121:66–72
pubmed: 8539342
Paxinos C, Watson D (2005) The rat brain in stereotaxic coordinates. Elsevier/Academic Press, Amsterdam
Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM, Kennedy SH (2005) Deep brain stimulation for treatment-resistant depression. Neuron 45:651–660
pubmed: 15748841
Arai AC, Xia YF, Rogers G, Lynch G, Kessler M (2002) Benzamide-type AMPA receptor modulators form two subfamilies with distinct modes of action. J Pharmacol Exp Ther 303:1075–1085
pubmed: 12438530
Mul JD, Zheng J, Goodyear LJ (2016) Validity assessment of 5 day repeated forced-swim stress to model human depression in young-adult C57BL/6J and BALB/cJ mice. eNeuro 29:3
Mezadri TJ, Batista GM, Portes AC, Marino-Neto J, Lino-de-Oliveira C (2011) Repeated rat-forced swim test: reducing the number of animals to evaluate gradual effects of antidepressants. J Neurosci Methods 195:200–205
pubmed: 21167866
Gordillo-Salas M, Pilar-Cuéllar F, Auberson YP, Adell A (2018) Signaling pathways responsible for the rapid antidepressant-like effects of a GluN2A-preferring NMDA receptor antagonist. Transl Psychiatry 8:84
pubmed: 29666360
pmcid: 5904130
Lucas G, Rymar VV, Du J, Mnie-Filali O, Bisgaard C, Manta S, Lambas-Senas L, Wiborg O et al (2007) Serotonin4 (5-HT4) receptor agonists are putative antidepressants with a rapid onset of action. Neuron 55:712–725
pubmed: 17785179
Ramboz S, Oosting R, Amara DA, Kung HF, Blier P, Mendelsohn M, Mann JJ, Brunner D et al (1998) Serotonin receptor 1A knockout: an animal model of anxiety-related disorder. Proc Natl Acad Sci USA 95:14476–14481
pubmed: 9826725
pmcid: 24398
Richardson-Jones JW, Craige CP, Guiard BP, Stephen A, Metzger KL, Kung HF, Gardier AM, Dranovsky A et al (2010) 5-HT1A autoreceptor levels determine vulnerability to stress and response to antidepressants. Neuron 65:40–52
pubmed: 20152112
pmcid: 2941196
Bortolozzi A, Castañé A, Semakova J, Santana N, Alvarado G, Cortés R, Ferrés-Coy A, Fernández G et al (2012) Selective siRNA-mediated suppression of 5-HT1A autoreceptors evokes strong anti-depressant-like effects. Mol Psychiatry 17:612–623
pubmed: 21808255
Jedema HP, Moghaddam B (1994) Glutamatergic control of dopamine release during stress in the rat prefrontal cortex. J Neurochem 63:785–788
pubmed: 7518503
Covington HE 3rd, Lobo MK, Maze I, Vialou V, Hyman JM, Zaman S, LaPlant Q, Mouzon E et al (2010) Antidepressant effect of optogenetic stimulation of the medial prefrontal cortex. J Neurosci 30:16082–16090
pubmed: 21123555
pmcid: 3004756
Warden MR, Selimbeyoglu A, Mirzabekov JJ, Lo M, Thompson KR, Kim SY, Adhikari A, Tye KM et al (2012) A prefrontal cortex-brainstem neuronal projection that controls response to behavioural challenge. Nature 492:428–432
pubmed: 23160494
pmcid: 5929119
Chaudhury D, Walsh JJ, Friedman AK, Juarez B, Ku SM, Koo JW, Ferguson D, Tsai HC et al (2013) Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons. Nature 493:532–536
pubmed: 23235832
Lauterborn JC, Lynch G, Vanderklish P, Arai A, Gall CM (2000) Positive modulation of AMPA receptors increases neurotrophin expression by hippocampal and cortical neurons. J Neurosci 20:8–21
pubmed: 10627576
pmcid: 6774091
Mackowiak M, O'Neill MJ, Hicks CA, Bleakman D, Skolnick P (2002) An AMPA receptor potentiator modulates hippocampal expression of BDNF: an in vivo study. Neuropharmacology 43:1–10
pubmed: 12213254
Radin DP, Johnson S, Purcell R, Lippa AS (2018) Effects of chronic systemic low-impact ampakine treatment on neurotrophin expression in rat brain. Biomed Pharmacother 105:540–544
pubmed: 29886374
Nibuya M, Morinobu S, Duman RS (1995) Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci 15:7539–7547
pubmed: 7472505
pmcid: 6578063
Björkholm C, Monteggia LM (2016) BDNF - A key transducer of antidepressant effects. Neuropharmacology 102:72–79
pubmed: 26519901
Ramaker MJ, Dulawa SC (2017) Identifying fast-onset antidepressants using rodent models. Mol Psychiatry 22:656–665
pubmed: 28322276
Jourdi H, Hsu YT, Zhou M, Qin Q, Bi X, Baudry M (2009) Positive AMPA receptor modulation rapidly stimulates BDNF release and increases dendritic mRNA translation. J Neurosci 29:8688–8697
pubmed: 19587275
pmcid: 2761758
Nikonenko I, Boda B, Steen S, Knott G, Welker E, Muller D (2008) PSD-95 promotes synaptogenesis and multiinnervated spine formation through nitric oxide signaling. J Cell Biol 183:1115–1127
pubmed: 19075115
pmcid: 2600742
Svenningsson P, Kim Y, Warner-Schmidt J, Oh YS, Greengard P (2013) p11 and its role in depression and therapeutic responses to antidepressants. Nat Rev Neurosci 14:673–680
pubmed: 24002251
pmcid: 3933996
Warner-Schmidt JL, Schmidt EF, Marshall JJ, Rubin AJ, Arango-Lievano M, Kaplitt MG, Ibañez-Tallon I, Heintz N et al (2012) Cholinergic interneurons in the nucleus accumbens regulate depression-like behavior. Proc Natl Acad Sci USA 109:11360–11365
pubmed: 22733786
pmcid: 3396525
Svenningsson P, Chergui K, Rachleff I, Flajolet M, Zhang X, El Yacoubi M, Vaugeois JM, Nomikos GG et al (2006) Alterations in 5-HT1B receptor function by p11 in depression-like states. Science 311:77–80
pubmed: 16400147
Warner-Schmidt JL, Chen EY, Zhang X, Marshall JJ, Morozov A, Svenningsson P, Greengard P (2010) A role for p11 in the antidepressant action of brain-derived neurotrophic factor. Biol Psychiatry 68:528–535
pubmed: 20591415
pmcid: 2929288
®2015 Allen Institute for Brain Science. Allen Brain Atlas API. Available from: http://brain-map.org/api/index.html .
Schmidt EF, Warner-Schmidt JL, Otopalik BG, Pickett SB, Greengard P, Heintz N (2012) Identification of the cortical neurons that mediate antidepressant responses. Cell 149:1152–1163
pubmed: 22632977
pmcid: 3397430
Freudenberg F, Celikel T, Reif A (2015) The role of a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in depression: central mediators of pathophysiology and antidepressant activity? Neurosci Biobehav Rev 52:193–206
pubmed: 25783220
Martínez-Turrillas R, Del Río J, Frechilla D (2005) Sequential changes in BDNF mRNA expression and synaptic levels of AMPA receptor subunits in rat hippocampus after chronic antidepressant treatment. Neuropharmacology 49:1178–1188
pubmed: 16143352
Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, Li XY, Aghajanian G et al (2010) mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329:959–964
pubmed: 20724638
pmcid: 3116441
Duman RS, Shinohara R, Fogaça MV, Hare B (2019) Neurobiology of rapid-acting antidepressants: convergent effects on GluA1-synaptic function. Mol Psychiatry 24:1816–1832
pubmed: 30894661
pmcid: 6754322