Skip to content
2000
Volume 23, Issue 6
  • ISSN: 1570-159X
  • E-ISSN: 1875-6190

Abstract

Activity-regulated cytoskeleton-associated protein (aka activity-regulated gene Arg3.1) belongs to the effector gene family of the immediate early genes. This family encodes effector proteins, which act directly on cellular homeostasis and function. Arc/Arg3.1 is localized at dendritic processes, allowing the protein local synthesis on demand, and it is considered a reliable index of activity-dependent synaptic changes. Evidence also exists showing the critical role of Arc/Arg3.1 in memory processes. The high sensitivity to changes in neuronal activity, its specific localization as well as its involvement in long-term synaptic plasticity indeed make this effector gene a potential, critical target of the action of psychotropic drugs. In this review, we focus on antipsychotic and antidepressant drugs as well as on psychostimulants, which belong to the category of drugs of abuse but can also be used as drugs for specific disorders of the central nervous system (., Attention Deficit Hyperactivity Disorder). It is demonstrated that psychotropic drugs with different mechanisms of action converge on Arc/Arg3.1, providing a means whereby Arc/Arg3.1 synaptic modulation may contribute to their therapeutic activity. The potential translational implications for different neuropsychiatric conditions are also discussed, recognizing that the treatment of these disorders is indeed complex and involves the simultaneous regulation of several dysfunctional mechanisms.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cn/10.2174/011570159X338335240903075655
2024-10-25
2025-07-25

  • From This Site

    /content/journals/cn/10.2174/011570159X338335240903075655
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. LyfordG.L. YamagataK. KaufmannW.E. BarnesC.A. SandersL.K. CopelandN.G. GilbertD.J. JenkinsN.A. LanahanA.A. WorleyP.F. Arc, a growth factor and activity-regulated gene, encodes a novel cytoskeleton-associated protein that is enriched in neuronal dendrites.Neuron199514243344510.1016/0896‑6273(95)90299‑6 7857651
     [Google Scholar]
  2. ClaytonD.F. The genomic action potential.Neurobiol. Learn. Mem.200074318521610.1006/nlme.2000.3967 11031127
     [Google Scholar]
  3. StewardO. WallaceC.S. LyfordG.L. WorleyP.F. Synaptic activation causes the mRNA for the IEG Arc to localize selectively near activated postsynaptic sites on dendrites.Neuron199821474175110.1016/S0896‑6273(00)80591‑7 9808461
     [Google Scholar]
  4. WallaceC.S. LyfordG.L. WorleyP.F. StewardO. Differential intracellular sorting of immediate early gene mRNAs depends on signals in the mRNA sequence.J. Neurosci.1998181263510.1523/JNEUROSCI.18‑01‑00026.1998 9412483
     [Google Scholar]
  5. HuangF. ChotinerJ.K. StewardO. Actin polymerization and ERK phosphorylation are required for Arc/Arg3.1 mRNA targeting to activated synaptic sites on dendrites.J. Neurosci.200727349054906710.1523/JNEUROSCI.2410‑07.2007 17715342
     [Google Scholar]
  6. StewardO. WorleyP.F. A cellular mechanism for targeting newly synthesized mRNAs to synaptic sites on dendrites.Proc. Natl. Acad. Sci. USA200198137062706810.1073/pnas.131146398 11416188
     [Google Scholar]
  7. FarrisS. LewandowskiG. CoxC.D. StewardO. Selective localization of arc mRNA in dendrites involves activity- and translation-dependent mRNA degradation.J. Neurosci.201434134481449310.1523/JNEUROSCI.4944‑13.2014 24671994
     [Google Scholar]
  8. GreerP.L. HanayamaR. BloodgoodB.L. MardinlyA.R. LiptonD.M. FlavellS.W. KimT.K. GriffithE.C. WaldonZ. MaehrR. PloeghH.L. ChowdhuryS. WorleyP.F. SteenJ. GreenbergM.E. The Angelman Syndrome protein Ube3A regulates synapse development by ubiquitinating arc.Cell2010140570471610.1016/j.cell.2010.01.026 20211139
     [Google Scholar]
  9. OkunoH. AkashiK. IshiiY. Yagishita-KyoN. SuzukiK. NonakaM. KawashimaT. FujiiH. Takemoto-KimuraS. AbeM. NatsumeR. ChowdhuryS. SakimuraK. WorleyP.F. BitoH. Inverse synaptic tagging of inactive synapses via dynamic interaction of Arc/Arg3.1 with CaMKIIβ.Cell2012149488689810.1016/j.cell.2012.02.062 22579289
     [Google Scholar]
  10. ChowdhuryS. ShepherdJ.D. OkunoH. LyfordG. PetraliaR.S. PlathN. KuhlD. HuganirR.L. WorleyP.F. Arc/Arg3.1 interacts with the endocytic machinery to regulate AMPA receptor trafficking.Neuron200652344545910.1016/j.neuron.2006.08.033 17088211
     [Google Scholar]
  11. Rial VerdeE.M. Lee-OsbourneJ. WorleyP.F. MalinowR. ClineH.T. Increased expression of the immediate-early gene arc/arg3.1 reduces AMPA receptor-mediated synaptic transmission.Neuron200652346147410.1016/j.neuron.2006.09.031 17088212
     [Google Scholar]
  12. ShepherdJ.D. RumbaughG. WuJ. ChowdhuryS. PlathN. KuhlD. HuganirR.L. WorleyP.F. Arc/Arg3.1 mediates homeostatic synaptic scaling of AMPA receptors.Neuron200652347548410.1016/j.neuron.2006.08.034 17088213
     [Google Scholar]
  13. RodríguezJ.J. DaviesH.A. ErringtonM.L. VerkhratskyA. BlissT.V.P. StewartM.G. ARG3.1/ARC expression in hippocampal dentate gyrus astrocytes: ultrastructural evidence and co‐localization with glial fibrillary acidic protein.J. Cell. Mol. Med.200812267167810.1111/j.1582‑4934.2007.00105.x 18419604
     [Google Scholar]
  14. RodríguezJ.J. DaviesH.A. SilvaA.T. De SouzaI.E.J. PeddieC.J. ColyerF.M. LancashireC.L. FineA. ErringtonM.L. BlissT.V.P. StewartM.G. Long‐term potentiation in the rat dentate gyrus is associated with enhanced Arc/Arg3.1 protein expression in spines, dendrites and glia.Eur. J. Neurosci.20052192384239610.1111/j.1460‑9568.2005.04068.x 15932597
     [Google Scholar]
  15. FernándezE. CollinsM.O. FrankR.A.W. ZhuF. KopanitsaM.V. NithianantharajahJ. LemprièreS.A. FrickerD. ElsegoodK.A. McLaughlinC.L. CroningM.D.R. McleanC. ArmstrongJ.D. HillW.D. DearyI.J. CencelliG. BagniC. FromerM. PurcellS.M. PocklingtonA.J. ChoudharyJ.S. KomiyamaN.H. GrantS.G.N. Arc requires PSD95 for assembly into postsynaptic complexes involved with neural dysfunction and intelligence.Cell Rep.201721367969110.1016/j.celrep.2017.09.045 29045836
     [Google Scholar]
  16. AvalloneM. PardoJ. MergiyaT.F. RájováJ. RäsänenA. DavidssonM. ÅkerblomM. QuintinoL. KumarD. BramhamC.R. BjörklundT. Visualizing Arc protein dynamics and localization in the mammalian brain using AAV-mediated in situ gene labeling.Front. Mol. Neurosci.202316114078510.3389/fnmol.2023.1140785 37415832
     [Google Scholar]
  17. KorbE. WilkinsonC.L. DelgadoR.N. LoveroK.L. FinkbeinerS. Arc in the nucleus regulates PML-dependent GluA1 transcription and homeostatic plasticity.Nat. Neurosci.201316787488310.1038/nn.3429 23749147
     [Google Scholar]
  18. BloomerW.A.C. VanDongenH.M.A. VanDongenA.M.J. Activity-regulated cytoskeleton-associated protein Arc/Arg3.1 binds to spectrin and associates with nuclear promyelocytic leukemia (PML) bodies.Brain Res.20071153203310.1016/j.brainres.2007.03.079 17466953
     [Google Scholar]
  19. ChuangY.A. HuT.M. ChenC.H. HsuS.H. TsaiH.Y. ChengM.C. Rare mutations and hypermethylation of the ARC gene associated with schizophrenia.Schizophr. Res.20161762-310611310.1016/j.schres.2016.07.019 27464451
     [Google Scholar]
  20. GalloF.T. KatcheC. MoriciJ.F. MedinaJ.H. WeisstaubN.V. Immediate early genes, memory and psychiatric disorders: Focus on c-Fos, Egr1 and Arc.Front. Behav. Neurosci.2018127910.3389/fnbeh.2018.00079 29755331
     [Google Scholar]
  21. YakoutD.W. ShreeN. MabbA.M. Effect of pharmacological manipulations on Arc function.CRPHAR2021210001310.1016/j.crphar.2020.100013 34909648
     [Google Scholar]
  22. WuJ. PetraliaR.S. KurushimaH. PatelH. JungM. VolkL. ChowdhuryS. ShepherdJ.D. DehoffM. LiY. KuhlD. HuganirR.L. PriceD.L. ScannevinR. TroncosoJ.C. WongP.C. WorleyP.F. Arc/Arg3.1 regulates an endosomal pathway essential for activity-dependent β-amyloid generation.Cell2011147361562810.1016/j.cell.2011.09.036 22036569
     [Google Scholar]
  23. ChenY. WangX. XiaoB. LuoZ. LongH. Mechanisms and functions of activity-regulated cytoskeleton-associated protein in synaptic plasticity.Mol. Neurobiol.202360105738575410.1007/s12035‑023‑03442‑4 37338805
     [Google Scholar]
  24. FumagalliF. BedogniF. FrascaA. Di PasqualeL. RacagniG. RivaM.A. Corticostriatal up-regulation of activity-regulated cytoskeletal-associated protein expression after repeated exposure to cocaine.Mol. Pharmacol.20067051726173410.1124/mol.106.026302 16908598
     [Google Scholar]
  25. ZhangH. BramhamC.R. Arc/Arg3.1 function in long‐term synaptic plasticity: Emerging mechanisms and unresolved issues.Eur. J. Neurosci.20215486696671210.1111/ejn.14958 32888346
     [Google Scholar]
  26. EriksenM.S. BramhamC.R. Molecular physiology of Arc/Arg3.1: The oligomeric state hypothesis of synaptic plasticity.Acta Physiol. 20222363e1388610.1111/apha.13886 36073248
     [Google Scholar]
  27. KuipersS.D. TrentaniA. TironA. MaoX. KuhlD. BramhamC.R. BDNF-induced LTP is associated with rapid Arc/Arg3.1-dependent enhancement in adult hippocampal neurogenesis.Sci. Rep.2016612122210.1038/srep21222 26888068
     [Google Scholar]
  28. MessaoudiE. KanhemaT. SouléJ. TironA. DagyteG. da SilvaB. BramhamC.R. Sustained Arc/Arg3.1 synthesis controls long-term potentiation consolidation through regulation of local actin polymerization in the dentate gyrus in vivo.J. Neurosci.20072739104451045510.1523/JNEUROSCI.2883‑07.2007 17898216
     [Google Scholar]
  29. WaungM.W. PfeifferB.E. NosyrevaE.D. RonesiJ.A. HuberK.M. Rapid translation of Arc/Arg3.1 selectively mediates mGluR-dependent LTD through persistent increases in AMPAR endocytosis rate.Neuron2008591849710.1016/j.neuron.2008.05.014 18614031
     [Google Scholar]
  30. BramhamC.R. AlmeM.N. BittinsM. KuipersS.D. NairR.R. PaiB. PanjaD. SchubertM. SouleJ. TironA. WibrandK. The Arc of synaptic memory.Exp. Brain Res.2010200212514010.1007/s00221‑009‑1959‑2 19690847
     [Google Scholar]
  31. RenM. CaoV. YeY. ManjiH.K. WangK.H. Arc regulates experience-dependent persistent firing patterns in frontal cortex.J. Neurosci.201434196583659510.1523/JNEUROSCI.0167‑14.2014 24806683
     [Google Scholar]
  32. GaoX. Castro-GomezS. GrendelJ. GrafS. SüsensU. BinkleL. MenschingD. IsbrandtD. KuhlD. OhanaO. Arc/Arg3.1 mediates a critical period for spatial learning and hippocampal networks.Proc. Natl. Acad. Sci. USA201811549125311253610.1073/pnas.1810125115 30442670
     [Google Scholar]
  33. PlathN. OhanaO. DammermannB. ErringtonM.L. SchmitzD. GrossC. MaoX. EngelsbergA. MahlkeC. WelzlH. KobalzU. StawrakakisA. FernandezE. WaltereitR. Bick-SanderA. TherstappenE. CookeS.F. BlanquetV. WurstW. SalmenB. BöslM.R. LippH.P. GrantS.G.N. BlissT.V.P. WolferD.P. KuhlD. Arc/Arg3.1 is essential for the consolidation of synaptic plasticity and memories.Neuron200652343744410.1016/j.neuron.2006.08.024 17088210
     [Google Scholar]
  34. GuzowskiJ.F. LyfordG.L. StevensonG.D. HoustonF.P. McGaughJ.L. WorleyP.F. BarnesC.A. Inhibition of activity-dependent arc protein expression in the rat hippocampus impairs the maintenance of long-term potentiation and the consolidation of long-term memory.J. Neurosci.200020113993400110.1523/JNEUROSCI.20‑11‑03993.2000 10818134
     [Google Scholar]
  35. NewpherT.M. HarrisS. PringleJ. HamiltonC. SoderlingS. Regulation of spine structural plasticity by Arc/Arg3.1.Semin. Cell Dev. Biol.201877253210.1016/j.semcdb.2017.09.022 28943393
     [Google Scholar]
  36. PastuzynE.D. DayC.E. KearnsR.B. Kyrke-SmithM. TaibiA.V. McCormickJ. YoderN. BelnapD.M. ErlendssonS. MoradoD.R. BriggsJ.A.G. FeschotteC. ShepherdJ.D. The neuronal gene arc encodes a repurposed retrotransposon gag protein that mediates intercellular RNA transfer.Cell20181721-2275288.e1810.1016/j.cell.2017.12.024 29328916
     [Google Scholar]
  37. JenksK.R. KimT. PastuzynE.D. OkunoH. TaibiA.V. BitoH. BearM.F. ShepherdJ.D. Arc restores juvenile plasticity in adult mouse visual cortex.Proc. Natl. Acad. Sci. USA2017114349182918710.1073/pnas.1700866114 28790183
     [Google Scholar]
  38. CookeS.F. BearM.F. How the mechanisms of long-term synaptic potentiation and depression serve experience-dependent plasticity in primary visual cortex.Philos. Trans. R. Soc. Lond. B Biol. Sci.201436916332013028410.1098/rstb.2013.0284 24298166
     [Google Scholar]
  39. Maya VetencourtJ.F. SaleA. ViegiA. BaroncelliL. De PasqualeR. O’LearyO.F. CastrénE. MaffeiL. The antidepressant fluoxetine restores plasticity in the adult visual cortex.Science2008320587438538810.1126/science.1150516 18420937
     [Google Scholar]
  40. ChiaC. OttoT. Hippocampal Arc (Arg3.1) expression is induced by memory recall and required for memory reconsolidation in trace fear conditioning.Neurobiol. Learn. Mem.2013106485510.1016/j.nlm.2013.06.021 23872190
     [Google Scholar]
  41. NakayamaD. IwataH. TeshirogiC. IkegayaY. MatsukiN. NomuraH. Long-delayed expression of the immediate early gene Arc/Arg3.1 refines neuronal circuits to perpetuate fear memory.J. Neurosci.201535281983010.1523/JNEUROSCI.2525‑14.2015 25589774
     [Google Scholar]
  42. GheidiA. DamphousseC.C. MarroneD.F. Experience-dependent persistent Arc expression is reduced in the aged hippocampus.Neurobiol. Aging20209522523010.1016/j.neurobiolaging.2020.07.032 32861833
     [Google Scholar]
  43. PloskiJ.E. PierreV.J. SmucnyJ. ParkK. MonseyM.S. OvereemK.A. SchafeG.E. The activity-regulated cytoskeletal-associated protein (Arc/Arg3.1) is required for memory consolidation of pavlovian fear conditioning in the lateral amygdala.J. Neurosci.20082847123831239510.1523/JNEUROSCI.1662‑08.2008 19020031
     [Google Scholar]
  44. MyrumC. GiddaluruS. JacobsenK. EspesethT. NybergL. LundervoldA.J. HaavikJ. NilssonL.G. ReinvangI. SteenV.M. JohanssonS. WibrandK. Le HellardS. BramhamC.R. Common variants in the ARC gene are not associated with cognitive abilities.Brain Behav.2015510e0037610.1002/brb3.376 26516611
     [Google Scholar]
  45. PurcellS.M. MoranJ.L. FromerM. RuderferD. SolovieffN. RoussosP. O’DushlaineC. ChambertK. BergenS.E. KählerA. DuncanL. StahlE. GenoveseG. FernándezE. CollinsM.O. KomiyamaN.H. ChoudharyJ.S. MagnussonP.K.E. BanksE. ShakirK. GarimellaK. FennellT. DePristoM. GrantS.G.N. HaggartyS.J. GabrielS. ScolnickE.M. LanderE.S. HultmanC.M. SullivanP.F. McCarrollS.A. SklarP. A polygenic burden of rare disruptive mutations in schizophrenia.Nature2014506748718519010.1038/nature12975 24463508
     [Google Scholar]
  46. FromerM. PocklingtonA.J. KavanaghD.H. WilliamsH.J. DwyerS. GormleyP. GeorgievaL. ReesE. PaltaP. RuderferD.M. CarreraN. HumphreysI. JohnsonJ.S. RoussosP. BarkerD.D. BanksE. MilanovaV. GrantS.G. HannonE. RoseS.A. ChambertK. MahajanM. ScolnickE.M. MoranJ.L. KirovG. PalotieA. McCarrollS.A. HolmansP. SklarP. OwenM.J. PurcellS.M. O’DonovanM.C. De novo mutations in schizophrenia implicate synaptic networks.Nature2014506748717918410.1038/nature12929 24463507
     [Google Scholar]
  47. ZhangW. WuJ. WardM.D. YangS. ChuangY.A. XiaoM. LiR. LeahyD.J. WorleyP.F. Structural basis of arc binding to synaptic proteins: Implications for cognitive disease.Neuron201586249050010.1016/j.neuron.2015.03.030 25864631
     [Google Scholar]
  48. Guillozet-BongaartsA.L. HydeT.M. DalleyR.A. HawrylyczM.J. HenryA. HofP.R. HohmannJ. JonesA.R. KuanC.L. RoyallJ. ShenE. SwansonB. ZengH. KleinmanJ.E. Altered gene expression in the dorsolateral prefrontal cortex of individuals with schizophrenia.Mol. Psychiatry201419447848510.1038/mp.2013.30 23528911
     [Google Scholar]
  49. HuentelmanM.J. MuppanaL. CorneveauxJ.J. DinuV. PruzinJ.J. ReimanR. BorishC.N. De BothM. AhmedA. TodorovA. CloningerC.R. ZhangR. MaJ. GallitanoA.L. Association of SNPs in EGR3 and ARC with Schizophrenia Supports a Biological Pathway for Schizophrenia Risk.PLoS One20151010e013507610.1371/journal.pone.0135076 26474411
     [Google Scholar]
  50. MarshallC.R. HowriganD.P. MericoD. ThiruvahindrapuramB. WuW. GreerD.S. AntakiD. ShettyA. HolmansP.A. PintoD. GujralM. BrandlerW.M. MalhotraD. WangZ. FajaradoK.V.F. MaileM.S. RipkeS. AgartzI. AlbusM. AlexanderM. AminF. AtkinsJ. BacanuS.A. BelliveauR.A.Jr BergenS.E. BertalanM. BevilacquaE. BigdeliT.B. BlackD.W. BruggemanR. BuccolaN.G. BucknerR.L. Bulik-SullivanB. ByerleyW. CahnW. CaiG. CairnsM.J. CampionD. CantorR.M. CarrV.J. CarreraN. CattsS.V. ChambertK.D. ChengW. CloningerC.R. CohenD. CormicanP. CraddockN. Crespo-FacorroB. CrowleyJ.J. CurtisD. DavidsonM. DavisK.L. DegenhardtF. Del FaveroJ. DeLisiL.E. DikeosD. DinanT. DjurovicS. DonohoeG. DrapeauE. DuanJ. DudbridgeF. EichhammerP. ErikssonJ. Escott-PriceV. EssiouxL. FanousA.H. FarhK.H. FarrellM.S. FrankJ. FrankeL. FreedmanR. FreimerN.B. FriedmanJ.I. ForstnerA.J. FromerM. GenoveseG. GeorgievaL. GershonE.S. GieglingI. Giusti-RodríguezP. GodardS. GoldsteinJ.I. GrattenJ. de HaanL. HamshereM.L. HansenM. HansenT. HaroutunianV. HartmannA.M. HenskensF.A. HermsS. HirschhornJ.N. HoffmannP. HofmanA. HuangH. IkedaM. JoaI. KählerA.K. KahnR.S. KalaydjievaL. KarjalainenJ. KavanaghD. KellerM.C. KellyB.J. KennedyJ.L. KimY. KnowlesJ.A. KonteB. LaurentC. LeeP. LeeS.H. LeggeS.E. LererB. LevyD.L. LiangK.Y. LiebermanJ. LönnqvistJ. LoughlandC.M. MagnussonP.K.E. MaherB.S. MaierW. MalletJ. MattheisenM. MattingsdalM. McCarleyR.W. McDonaldC. McIntoshA.M. MeierS. MeijerC.J. MelleI. Mesholam-GatelyR.I. MetspaluA. MichieP.T. MilaniL. MilanovaV. MokrabY. MorrisD.W. Müller-MyhsokB. MurphyK.C. MurrayR.M. Myin-GermeysI. NenadicI. NertneyD.A. NestadtG. NicodemusK.K. NisenbaumL. NordinA. O’CallaghanE. O’DushlaineC. OhS.Y. OlincyA. OlsenL. O’NeillF.A. Van OsJ. PantelisC. PapadimitriouG.N. ParkhomenkoE. PatoM.T. PaunioT. PerkinsD.O. PersT.H. PietiläinenO. PimmJ. PocklingtonA.J. PowellJ. PriceA. PulverA.E. PurcellS.M. QuestedD. RasmussenH.B. ReichenbergA. ReimersM.A. RichardsA.L. RoffmanJ.L. RoussosP. RuderferD.M. SalomaaV. SandersA.R. SavitzA. SchallU. SchulzeT.G. SchwabS.G. ScolnickE.M. ScottR.J. SeidmanL.J. ShiJ. SilvermanJ.M. SmollerJ.W. SödermanE. SpencerC.C.A. StahlE.A. StrengmanE. StrohmaierJ. StroupT.S. SuvisaariJ. SvrakicD.M. SzatkiewiczJ.P. ThirumalaiS. TooneyP.A. VeijolaJ. VisscherP.M. WaddingtonJ. WalshD. WebbB.T. WeiserM. WildenauerD.B. WilliamsN.M. WilliamsS. WittS.H. WolenA.R. WormleyB.K. WrayN.R. WuJ.Q. ZaiC.C. AdolfssonR. AndreassenO.A. BlackwoodD.H.R. BramonE. BuxbaumJ.D. CichonS. CollierD.A. CorvinA. DalyM.J. DarvasiA. DomeniciE. EskoT. GejmanP.V. GillM. GurlingH. HultmanC.M. IwataN. JablenskyA.V. JönssonE.G. KendlerK.S. KirovG. KnightJ. LevinsonD.F. LiQ.S. McCarrollS.A. McQuillinA. MoranJ.L. MowryB.J. NöthenM.M. OphoffR.A. OwenM.J. PalotieA. PatoC.N. PetryshenT.L. PosthumaD. RietschelM. RileyB.P. RujescuD. SklarP. St ClairD. WaltersJ.T.R. WergeT. SullivanP.F. O’DonovanM.C. SchererS.W. NealeB.M. SebatJ. Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects.Nat. Genet.2017491273510.1038/ng.3725 27869829
     [Google Scholar]
  51. TakagiS. BaluD.T. CoyleJ.T. Subchronic pharmacological and chronic genetic NMDA receptor hypofunction differentially regulate the Akt signaling pathway and Arc expression in juvenile and adult mice.Schizophr. Res.20151621-321622110.1016/j.schres.2014.12.034 25592804
     [Google Scholar]
  52. ThomsenM.S. HansenH.H. MikkelsenJ.D. Opposite effect of phencyclidine on activity-regulated cytoskeleton-associated protein (Arc) in juvenile and adult limbic rat brain regions.Neurochem. Int.201056227027510.1016/j.neuint.2009.10.011 19897002
     [Google Scholar]
  53. ManagòF. MereuM. MastwalS. MastrogiacomoR. ScheggiaD. EmanueleM. De LucaM.A. WeinbergerD.R. WangK.H. PapaleoF. Genetic disruption of Arc/Arg3.1 in mice causes alterations in dopamine and neurobehavioral phenotypes related to schizophrenia.Cell Rep.20161682116212810.1016/j.celrep.2016.07.044 27524619
     [Google Scholar]
  54. FumagalliF. FrascaA. RacagniG. RivaM.A. Antipsychotic drugs modulate Arc expression in the rat brain.Eur. Neuropsychopharmacol.200919210911510.1016/j.euroneuro.2008.09.001 18947986
     [Google Scholar]
  55. ZhengP. HuM. XieY. YuY. Jaaro-PeledH. HuangX.F. Aripiprazole and haloperidol protect neurite lesions via reducing excessive D2R-DISC1 complex formation.Prog. Neuropsychopharmacol. Biol. Psychiatry201992596910.1016/j.pnpbp.2018.12.007 30597182
     [Google Scholar]
  56. ManagòF. PapaleoF. Schizophrenia: What’s Arc Got to Do with It?Front. Behav. Neurosci.20171118110.3389/fnbeh.2017.00181 28979198
     [Google Scholar]
  57. BamfordN.S. ZhangH. SchmitzY. WuN.P. CepedaC. LevineM.S. SchmaussC. ZakharenkoS.S. ZablowL. SulzerD. Heterosynaptic dopamine neurotransmission selects sets of corticostriatal terminals.Neuron200442465366310.1016/S0896‑6273(04)00265‑X 15157425
     [Google Scholar]
  58. YinH.H. LovingerD.M. Frequency-specific and D2 receptor-mediated inhibition of glutamate release by retrograde endocannabinoid signaling.Proc. Natl. Acad. Sci. USA2006103218251825610.1073/pnas.0510797103 16698932
     [Google Scholar]
  59. SurmeierD.J. DingJ. DayM. WangZ. ShenW. D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons.Trends Neurosci.200730522823510.1016/j.tins.2007.03.008 17408758
     [Google Scholar]
  60. CepedaC. LevineM.S. Dopamine and N-methyl-D-aspartate receptor interactions in the neostriatum.Dev. Neurosci.199820111810.1159/000017294 9600386
     [Google Scholar]
  61. PetterssonF. PonténH. WatersN. WatersS. SonessonC. Synthesis and evaluation of a set of 4-phenylpiperidines and 4-phenylpiperazines as D2 receptor ligands and the discovery of the dopaminergic stabilizer 4-[3-(methylsulfonyl)phenyl]-1-propylpiperidine (huntexil, pridopidine, ACR16).J. Med. Chem.20105362510252010.1021/jm901689v 20155917
     [Google Scholar]
  62. WatersS. PontenH. EdlingM. SvanbergB. KlamerD. WatersN. The dopaminergic stabilizers pridopidine and ordopidine enhance cortico-striatal Arc gene expression.J. Neural Transm. 2014121111337134710.1007/s00702‑014‑1231‑1 24817271
     [Google Scholar]
  63. GronierB. WatersS. PontenH. The dopaminergic stabilizer pridopidine increases neuronal activity of pyramidal neurons in the prefrontal cortex.J. Neural Transm. 201312091281129410.1007/s00702‑013‑1002‑4 23468085
     [Google Scholar]
  64. SeamansJ.K. DurstewitzD. ChristieB.R. StevensC.F. SejnowskiT.J. Dopamine D1/D5 receptor modulation of excitatory synaptic inputs to layer V prefrontal cortex neurons.Proc. Natl. Acad. Sci. USA200198130130610.1073/pnas.98.1.301 11134516
     [Google Scholar]
  65. SolmiM. MurruA. PacchiarottiI. UndurragaJ. VeroneseN. FornaroM. StubbsB. MonacoF. VietaE. SeemanM. CorrellC. CarvalhoA. Safety, tolerability, and risks associated with first- and second-generation antipsychotics: A state-of-the-art clinical review.Ther. Clin. Risk Manag.20171375777710.2147/TCRM.S117321 28721057
     [Google Scholar]
  66. KapurS. SeemanP. Antipsychotic agents differ in how fast they come off the dopamine D2 receptors. Implications for atypical antipsychotic action.J. Psychiatry Neurosci.2000252161166 10740989
     [Google Scholar]
  67. HomayounH. MoghaddamB. Fine-tuning of awake prefrontal cortex neurons by clozapine: Comparison with haloperidol and N-desmethylclozapine.Biol. Psychiatry200761567968710.1016/j.biopsych.2006.05.016 17046721
     [Google Scholar]
  68. LecrubierY. Is amisulpride an ‘atypical’ atypical antipsychotic agent?Int. Clin. Psychopharmacol.200015Suppl. 4S21S26 11252520
     [Google Scholar]
  69. de BartolomeisA. MarmoF. BuonaguroE.F. RossiR. TomasettiC. IasevoliF. Imaging brain gene expression profiles by antipsychotics: Region-specific action of amisulpride on postsynaptic density transcripts compared to haloperidol.Eur. Neuropsychopharmacol.201323111516152910.1016/j.euroneuro.2012.11.014 23357084
     [Google Scholar]
  70. LuoniA. RochaF.F. RivaM.A. Anatomical specificity in the modulation of activity-regulated genes after acute or chronic lurasidone treatment.Prog. Neuropsychopharmacol. Biol. Psychiatry2014509410110.1016/j.pnpbp.2013.12.008 24361635
     [Google Scholar]
  71. ShahidM. WalkerG.B. ZornS.H. WongE. Asenapine: A novel psychopharmacologic agent with a unique human receptor signature.J. Psychopharmacol.2009231657310.1177/0269881107082944 18308814
     [Google Scholar]
  72. de BartolomeisA. IasevoliF. MarmoF. BuonaguroE.F. EramoA. RossiR. AvvisatiL. LatteG. TomasettiC. Progressive recruitment of cortical and striatal regions by inducible postsynaptic density transcripts after increasing doses of antipsychotics with different receptor profiles: Insights for psychosis treatment.Eur. Neuropsychopharmacol.201525456658210.1016/j.euroneuro.2015.01.003 25649681
     [Google Scholar]
  73. FrånbergO. MarcusM.M. IvanovV. SchilströmB. ShahidM. SvenssonT.H. Asenapine elevates cortical dopamine, noradrenaline and serotonin release. Evidence for activation of cortical and subcortical dopamine systems by different mechanisms.Psychopharmacology 2009204225126410.1007/s00213‑008‑1456‑5 19198810
     [Google Scholar]
  74. ArntJ. SkarsfeldtT. Do novel antipsychotics have similar pharmacological characteristics? A review of the evidence.Neuropsychopharmacology19981826310110.1016/S0893‑133X(97)00112‑7 9430133
     [Google Scholar]
  75. IasevoliF. TomasettiC. MarmoF. BraviD. ArntJ. de BartolomeisA. Divergent acute and chronic modulation of glutamatergic postsynaptic density genes expression by the antipsychotics haloperidol and sertindole.Psychopharmacology 2010212332934410.1007/s00213‑010‑1954‑0 20652539
     [Google Scholar]
  76. DedicN. JonesP.G. HopkinsS.C. LewR. ShaoL. CampbellJ.E. SpearK.L. LargeT.H. CampbellU.C. HananiaT. LeahyE. KoblanK.S. SEP-363856, a novel psychotropic agent with a unique, non-D2 receptor mechanism of action.J. Pharmacol. Exp. Ther.2019371111410.1124/jpet.119.260281 31371483
     [Google Scholar]
  77. BegniV. SansonA. LuoniA. SensiniF. GraysonB. MunniS. NeillJ.C. RivaM.A. Towards novel treatments for Schizophrenia: Molecular and behavioural signatures of the psychotropic agent SEP-363856.Int. J. Mol. Sci.2021228411910.3390/ijms22084119 33923479
     [Google Scholar]
  78. Bruins SlotL.A. LestienneF. Grevoz-BarretC. Newman-TancrediA. CussacD. F15063, a potential antipsychotic with dopamine D2/D3 receptor antagonist and 5-HT1A receptor agonist properties: Influence on immediate-early gene expression in rat prefrontal cortex and striatum.Eur. J. Pharmacol.20096201-3273510.1016/j.ejphar.2009.08.019 19695244
     [Google Scholar]
  79. CollinsC.M. WoodM.D. ElliottJ.M. Chronic administration of haloperidol and clozapine induces differential effects on the expression of Arc and c-Fos in rat brain.J. Psychopharmacol.2014281094795410.1177/0269881114536788 24989643
     [Google Scholar]
  80. BuonaguroE.F. IasevoliF. MarmoF. EramoA. LatteG. AvaglianoC. TomasettiC. de BartolomeisA. Re-arrangements of gene transcripts at glutamatergic synapses after prolonged treatments with antipsychotics: A putative link with synaptic remodeling.Prog. Neuropsychopharmacol. Biol. Psychiatry201776294110.1016/j.pnpbp.2017.02.012 28235555
     [Google Scholar]
  81. FumagalliF. FrascaA. RacagniG. RivaM.A. Dynamic regulation of glutamatergic postsynaptic activity in rat prefrontal cortex by repeated administration of antipsychotic drugs.Mol. Pharmacol.20087351484149010.1124/mol.107.043786 18250147
     [Google Scholar]
  82. PeiQ. TorderaR. SprakesM. SharpT. Glutamate receptor activation is involved in 5-HT2 agonist-induced Arc gene expression in the rat cortex.Neuropharmacology200446333133910.1016/j.neuropharm.2003.09.017 14975688
     [Google Scholar]
  83. KesslerR.M. AnsariM.S. RiccardiP. LiR. JayathilakeK. DawantB. MeltzerH.Y. Occupancy of striatal and extrastriatal dopamine D2 receptors by clozapine and quetiapine.Neuropsychopharmacology20063191991200110.1038/sj.npp.1301108 16738543
     [Google Scholar]
  84. DonaiH. SugiuraH. AraD. YoshimuraY. YamagataK. YamauchiT. Interaction of Arc with CaM kinase II and stimulation of neurite extension by Arc in neuroblastoma cells expressing CaM kinase II.Neurosci. Res.200347439940810.1016/j.neures.2003.08.004 14630344
     [Google Scholar]
  85. VazdarjanovaA. Ramirez-AmayaV. InselN. PlummerT.K. RosiS. ChowdhuryS. MikhaelD. WorleyP.F. GuzowskiJ.F. BarnesC.A. Spatial exploration induces ARC, a plasticity‐related immediate‐early gene, only in calcium/calmodulin‐dependent protein kinase II‐positive principal excitatory and inhibitory neurons of the rat forebrain.J. Comp. Neurol.2006498331732910.1002/cne.21003 16871537
     [Google Scholar]
  86. GardoniF. FrascaA. ZianniE. RivaM.A. Di LucaM. FumagalliF. Repeated treatment with haloperidol, but not olanzapine, alters synaptic NMDA receptor composition in rat striatum.Eur. Neuropsychopharmacol.200818753153410.1016/j.euroneuro.2007.10.004 18061412
     [Google Scholar]
  87. LuoniA. FumagalliF. RacagniG. RivaM.A. Repeated aripiprazole treatment regulates Bdnf, Arc and Npas4 expression under basal condition as well as after an acute swim stress in the rat brain.Pharmacol. Res.2014801810.1016/j.phrs.2013.11.008 24309096
     [Google Scholar]
  88. MolteniR. CalabreseF. RacagniG. FumagalliF. RivaM.A. Antipsychotic drug actions on gene modulation and signaling mechanisms.Pharmacol. Ther.20091241748510.1016/j.pharmthera.2009.06.001 19540875
     [Google Scholar]
  89. IasevoliF. TomasettiC. de BartolomeisA. Scaffolding proteins of the post-synaptic density contribute to synaptic plasticity by regulating receptor localization and distribution: Relevance for neuropsychiatric diseases.Neurochem. Res.201338112210.1007/s11064‑012‑0886‑y 22991141
     [Google Scholar]
  90. BymasterF.P. Hemrick-LueckeS.K. PerryK.W. FullerR.W. Neurochemical evidence for antagonism by olanzapine of dopamine, serotonin, α1-adrenergic and muscarinic receptors in vivo in rats.Psychopharmacology 19961241-2879410.1007/BF02245608 8935803
     [Google Scholar]
  91. TaraziF.I. StahlS.M. Iloperidone, asenapine and lurasidone: A primer on their current status.Expert Opin. Pharmacother.201213131911192210.1517/14656566.2012.712114 22849428
     [Google Scholar]
  92. TokarskiK. BobulaB. Grzegorzewska-HiczwaM. KusekM. HessG. Stress- and antidepressant treatment-induced modifications of 5-HT7 receptor functions in the rat brain.Pharmacol. Rep.20126461305131510.1016/S1734‑1140(12)70928‑3 23406741
     [Google Scholar]
  93. PeiQ. ZetterströmT.S.C. SprakesM. TorderaR. SharpT. Antidepressant drug treatment induces Arc gene expression in the rat brain.Neuroscience2003121497598210.1016/S0306‑4522(03)00504‑9 14580947
     [Google Scholar]
  94. MolteniR. CalabreseF. ManciniM. RacagniG. RivaM.A. Basal and stress-induced modulation of activity-regulated cytoskeletal associated protein (Arc) in the rat brain following duloxetine treatment.Psychopharmacology 2008201228529210.1007/s00213‑008‑1276‑7 18704370
     [Google Scholar]
  95. FumagalliF. CalabreseF. LuoniA. BolisF. RacagniG. RivaM.A. Modulation of BDNF expression by repeated treatment with the novel antipsychotic lurasidone under basal condition and in response to acute stress.Int. J. Neuropsychopharmacol.201215223524610.1017/S1461145711000150 21349227
     [Google Scholar]
  96. KishiT. MatsudaY. NakamuraH. IwataN. Blonanserin for schizophrenia: Systematic review and meta-analysis of double-blind, randomized, controlled trials.J. Psychiatr. Res.201347214915410.1016/j.jpsychires.2012.10.011 23131856
     [Google Scholar]
  97. PaladiniM.S. SperoV. BegniV. MarchisellaF. GuidiA. GrucaP. LasonM. LitwaE. PappM. RivaM.A. MolteniR. Behavioral and molecular effects of the antipsychotic drug blonanserin in the chronic mild stress model.Pharmacol. Res.202116310533010.1016/j.phrs.2020.105330 33276101
     [Google Scholar]
  98. MarchisellaF. PaladiniM.S. GuidiA. BegniV. BrivioP. SperoV. CalabreseF. MolteniR. RivaM.A. Chronic treatment with the antipsychotic drug blonanserin modulates the responsiveness to acute stress with anatomical selectivity.Psychopharmacology 202023761783179310.1007/s00213‑020‑05498‑9 32296859
     [Google Scholar]
  99. NakaharaT. KurokiT. HashimotoK. HondoH. TsutsumiT. MotomuraK. UekiH. HiranoM. UchimuraH. Effect of atypical antipsychotics on phencyclidine-induced expression of arc in rat brain.Neuroreport200011355155510.1097/00001756‑200002280‑00025 10718313
     [Google Scholar]
  100. FumagalliF. MolteniR. RoceriM. BedogniF. SanteroR. FossatiC. GennarelliM. RacagniG. RivaM.A. Effect of antipsychotic drugs on brain‐derived neurotrophic factor expression under reduced N‐methyl‐D‐aspartate receptor activity.J. Neurosci. Res.200372562262810.1002/jnr.10609 12749027
     [Google Scholar]
  101. MolteniR. CalabreseF. MajP.F. OlivierJ.D.A. RacagniG. EllenbroekB.A. RivaM.A. Altered expression and modulation of activity-regulated cytoskeletal associated protein (Arc) in serotonin transporter knockout rats.Eur. Neuropsychopharmacol.2009191289890410.1016/j.euroneuro.2009.06.008 19576731
     [Google Scholar]
  102. ErikssonT.M. DelagrangeP. SpeddingM. PopoliM. MathéA.A. ÖgrenS.O. SvenningssonP. Emotional memory impairments in a genetic rat model of depression: involvement of 5-HT/MEK/Arc signaling in restoration.Mol. Psychiatry201217217318410.1038/mp.2010.131 21242991
     [Google Scholar]
  103. GammieS.C. Evaluation of animal model congruence to human depression based on large-scale gene expression patterns of the CNS.Sci. Rep.202212110810.1038/s41598‑021‑04020‑1 34997033
     [Google Scholar]
  104. de FoubertG. CarneyS.L. RobinsonC.S. DestexheE.J. TomlinsonR. HicksC.A. MurrayT.K. GaillardJ.P. DevilleC. XhensevalV. ThomasC.E. O’NeillM.J. ZetterströmT.S.C. Fluoxetine-induced change in rat brain expression of brain-derived neurotrophic factor varies depending on length of treatment.Neuroscience2004128359760410.1016/j.neuroscience.2004.06.054 15381288
     [Google Scholar]
  105. AlmeM.N. WibrandK. DagestadG. BramhamC.R. Chronic fluoxetine treatment induces brain region-specific upregulation of genes associated with BDNF-induced long-term potentiation.Neural Plast.200720071910.1155/2007/26496 18301726
     [Google Scholar]
  106. Bang-AndersenB. RuhlandT. JørgensenM. SmithG. FrederiksenK. JensenK.G. ZhongH. NielsenS.M. HoggS. MørkA. StensbølT.B. 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.20115493206322110.1021/jm101459g 21486038
     [Google Scholar]
  107. BrivioP. CorsiniG. RivaM.A. CalabreseF. Chronic vortioxetine treatment improves the responsiveness to an acute stress acting through the ventral hippocampus in a glucocorticoid-dependent way.Pharmacol. Res.2019142142110.1016/j.phrs.2019.02.006 30735803
     [Google Scholar]
  108. HenkeP.G. Hippocampal pathway to the amygdala and stress ulcer development.Brain Res. Bull.199025569169510.1016/0361‑9230(90)90044‑Z 2289157
     [Google Scholar]
  109. El MansariM. LecoursM. BlierP. Effects of acute and sustained administration of vortioxetine on the serotonin system in the hippocampus: Electrophysiological studies in the rat brain.Psychopharmacology 2015232132343235210.1007/s00213‑015‑3870‑9 25665528
     [Google Scholar]
  110. PehrsonA.L. CremersT. BétryC. van der HartM.G.C. JørgensenL. MadsenM. HaddjeriN. EbertB. SanchezC. Lu AA21004, a novel multimodal antidepressant, produces regionally selective increases of multiple neurotransmitters—A rat microdialysis and electrophysiology study.Eur. Neuropsychopharmacol.201323213314510.1016/j.euroneuro.2012.04.006 22612991
     [Google Scholar]
  111. CastrénE. Is mood chemistry?Nat. Rev. Neurosci.20056324124610.1038/nrn1629 15738959
     [Google Scholar]
  112. KugathasanP. WallerJ. WestrichL. AbdourahmanA. TammJ.A. PehrsonA.L. DaleE. GulinelloM. SanchezC. LiY. In vivo and in vitro effects of vortioxetine on molecules associated with neuroplasticity.J. Psychopharmacol.201731336537610.1177/0269881116667710 27678087
     [Google Scholar]
  113. DaleE. ZhangH. LeiserS.C. XiaoY. LuD. YangC.R. PlathN. SanchezC. Vortioxetine disinhibits pyramidal cell function and enhances synaptic plasticity in the rat hippocampus.J. Psychopharmacol.2014281089190210.1177/0269881114543719 25122043
     [Google Scholar]
  114. LiY. PehrsonA.L. WallerJ.A. DaleE. SanchezC. GulinelloM. A critical evaluation of the activity-regulated cytoskeleton-associated protein (Arc/Arg3.1)'s putative role in regulating dendritic plasticity, cognitive processes, and mood in animal models of depression.Front. Neurosci.2015927910.3389/fnins.2015.00279 26321903
     [Google Scholar]
  115. SanchezC. AsinK.E. ArtigasF. Vortioxetine, a novel antidepressant with multimodal activity: Review of preclinical and clinical data.Pharmacol. Ther.2015145435710.1016/j.pharmthera.2014.07.001 25016186
     [Google Scholar]
  116. BymasterF. LeeT. KnadlerM. DetkeM. IyengarS. The dual transporter inhibitor duloxetine: A review of its preclinical pharmacology, pharmacokinetic profile, and clinical results in depression.Curr. Pharm. Des.200511121475149310.2174/1381612053764805 15892657
     [Google Scholar]
  117. CoutensB. YrondiA. RamponC. GuiardB.P. Psychopharmacological properties and therapeutic profile of the antidepressant venlafaxine.Psychopharmacology 202223992735275210.1007/s00213‑022‑06203‑8 35947166
     [Google Scholar]
  118. SerresF. MillanM.J. SharpT. Molecular adaptation to chronic antidepressant treatment: evidence for a more rapid response to the novel α2-adrenoceptor antagonist/5-HT-noradrenaline reuptake inhibitor (SNRI), S35966, compared to the SNRI, venlafaxine.Int. J. Neuropsychopharmacol.201215561762910.1017/S1461145711000733 21733241
     [Google Scholar]
  119. BenedettiF. RadaelliD. BernasconiA. DallaspeziaS. ColomboC. SmeraldiE. Changes in medial prefrontal cortex neural responses parallel successful antidepressant combination of venlafaxine and light therapy.Arch. Ital. Biol.200914738393 20014654
     [Google Scholar]
  120. LiuR.J. AghajanianG.K. Stress blunts serotonin- and hypocretin-evoked EPSCs in prefrontal cortex: Role of corticosterone-mediated apical dendritic atrophy.Proc. Natl. Acad. Sci. USA2008105135936410.1073/pnas.0706679105 18172209
     [Google Scholar]
  121. BrivioP. GalloM.T. GrucaP. LasonM. LitwaE. FumagalliF. PappM. CalabreseF. Chronic N-acetyl-cysteine treatment enhances the expression of the immediate early gene nr4a1 in response to an acute challenge in male rats: Comparison with the antidepressant venlafaxine.Int. J. Mol. Sci.2023248732110.3390/ijms24087321 37108481
     [Google Scholar]
  122. CalabreseF. MolteniR. GabrielC. MocaerE. RacagniG. RivaM.A. Modulation of neuroplastic molecules in selected brain regions after chronic administration of the novel antidepressant agomelatine.Psychopharmacology 2011215226727510.1007/s00213‑010‑2129‑8 21181122
     [Google Scholar]
  123. BoulleF. MassartR. StragierE. PaïzanisE. ZaidanL. MardayS. GabrielC. MocaerE. MongeauR. LanfumeyL. Hippocampal and behavioral dysfunctions in a mouse model of environmental stress: Normalization by agomelatine.Transl. Psychiatry2014411e485e48510.1038/tp.2014.125 25423137
     [Google Scholar]
  124. MarballiK.K. GallitanoA.L. Immediate early genes anchor a biological pathway of proteins required for memory formation, long-term depression and risk for schizophrenia.Front. Behav. Neurosci.2018122310.3389/fnbeh.2018.00023 29520222
     [Google Scholar]
  125. NaY. ParkS. LeeC. KimD.K. ParkJ.M. SockanathanS. HuganirR.L. WorleyP.F. Real-time imaging reveals properties of glutamate-induced arc/arg 3.1 translation in neuronal dendrites.Neuron201691356157310.1016/j.neuron.2016.06.017 27397520
     [Google Scholar]
  126. PhamK. NacherJ. HofP.R. McEwenB.S. Repeated restraint stress suppresses neurogenesis and induces biphasic PSA‐NCAM expression in the adult rat dentate gyrus.Eur. J. Neurosci.200317487988610.1046/j.1460‑9568.2003.02513.x 12603278
     [Google Scholar]
  127. MirescuC. GouldE. Stress and adult neurogenesis.Hippocampus200616323323810.1002/hipo.20155 16411244
     [Google Scholar]
  128. SantarelliL. SaxeM. GrossC. SurgetA. BattagliaF. DulawaS. WeisstaubN. LeeJ. DumanR. ArancioO. BelzungC. HenR. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants.Science2003301563480580910.1126/science.1083328 12907793
     [Google Scholar]
  129. CasarottoP.C. GirychM. FredS.M. KovalevaV. MolinerR. EnkaviG. BiojoneC. CannarozzoC. SahuM.P. KaurinkoskiK. BrunelloC.A. SteinzeigA. WinkelF. PatilS. VestringS. SerchovT. DinizC.R.A.F. LaukkanenL. CardonI. AntilaH. RogT. PiepponenT.P. BramhamC.R. NormannC. LauriS.E. SaarmaM. VattulainenI. CastrénE. Antidepressant drugs act by directly binding to TRKB neurotrophin receptors.Cell2021184512991313.e1910.1016/j.cell.2021.01.034 33606976
     [Google Scholar]
  130. ReynoldsJ.N. BaskysA. CarlenP.L. The effects of serotonin on N-methyl-d-aspartate and synaptically evoked depolarizations in rat neocortical neurons.Brain Res.1988456228629210.1016/0006‑8993(88)90230‑2 3061564
     [Google Scholar]
  131. ChenT. ZhuJ. YangL.K. FengY. LinW. WangY.H. Glutamate-induced rapid induction of Arc/Arg3.1 requires NMDA receptor-mediated phosphorylation of ERK and CREB.Neurosci. Lett.2017661232810.1016/j.neulet.2017.09.024 28919534
     [Google Scholar]
  132. RéusG.Z. AbelairaH.M. AgostinhoF.R. RibeiroK.F. VittoM.F. LucianoT.F. de SouzaC.T. QuevedoJ. The administration of olanzapine and fluoxetine has synergistic effects on intracellular survival pathways in the rat brain.J. Psychiatr. Res.20124681029103510.1016/j.jpsychires.2012.04.016 22575330
     [Google Scholar]
  133. CaffinoL. MottarliniF. PivaA. RizziB. FumagalliF. ChiamuleraC. Temporal dynamics of BDNF signaling recruitment in the rat prefrontal cortex and hippocampus following a single infusion of a translational dose of ketamine.Neuropharmacology202424210976710.1016/j.neuropharm.2023.109767 37858883
     [Google Scholar]
  134. ParkS. ParkJ.M. KimS. KimJ.A. ShepherdJ.D. Smith-HicksC.L. ChowdhuryS. KaufmannW. KuhlD. RyazanovA.G. HuganirR.L. LindenD.J. WorleyP.F. Elongation factor 2 and fragile X mental retardation protein control the dynamic translation of Arc/Arg3.1 essential for mGluR-LTD.Neuron2008591708310.1016/j.neuron.2008.05.023 18614030
     [Google Scholar]
  135. RacagniG. RivaM.A. MolteniR. MusazziL. CalabreseF. PopoliM. TarditoD. Mode of action of agomelatine: Synergy between melatonergic and 5-HT 2C receptors.World J. Biol. Psychiatry201112857458710.3109/15622975.2011.595823 21999473
     [Google Scholar]
  136. CaffinoL. MessaG. FumagalliF. A single cocaine administration alters dendritic spine morphology and impairs glutamate receptor synaptic retention in the medial prefrontal cortex of adolescent rats.Neuropharmacology201814020921610.1016/j.neuropharm.2018.08.006 30092246
     [Google Scholar]
  137. CaffinoL. GiannottiG. RacagniG. FumagalliF. A single cocaine exposure disrupts actin dynamics in the cortico-accumbal pathway of adolescent rats: modulation by a second cocaine injection.Psychopharmacology 201723481217122210.1007/s00213‑017‑4559‑z 28204841
     [Google Scholar]
  138. SaleryM. Dos SantosM. Saint-JourE. MoumnéL. PagèsC. KappèsV. ParnaudeauS. CabocheJ. VanhoutteP. Activity-regulated cytoskeleton-associated protein accumulates in the nucleus in response to cocaine and acts as a brake on chromatin remodeling and long-term behavioral alterations.Biol. Psychiatry201781757358410.1016/j.biopsych.2016.05.025 27567310
     [Google Scholar]
  139. CaffinoL. GiannottiG. MottarliniF. RacagniG. FumagalliF. Developmental exposure to cocaine dynamically dysregulates cortical Arc/Arg3.1 modulation in response to a challenge.Neurotox. Res.201731228929710.1007/s12640‑016‑9683‑8 27832448
     [Google Scholar]
  140. CaffinoL. CalabreseF. GiannottiG. BarbonA. VerheijM.M.M. RacagniG. FumagalliF. Stress rapidly dysregulates the glutamatergic synapse in the prefrontal cortex of cocaine-withdrawn adolescent rats.Addict. Biol.201520115816910.1111/adb.12089 24102978
     [Google Scholar]
  141. BhatR.V. BarabanJ.M. Activation of transcription factor genes in striatum by cocaine: Role of both serotonin and dopamine systems.J. Pharmacol. Exp. Ther.19932671496505 8229780
     [Google Scholar]
  142. CovingtonH.E.III KikusuiT. GoodhueJ. NikulinaE.M. HammerR.P.Jr MiczekK.A. Brief social defeat stress: Long lasting effects on cocaine taking during a binge and zif268 mRNA expression in the amygdala and prefrontal cortex.Neuropsychopharmacology200530231032110.1038/sj.npp.1300587 15496936
     [Google Scholar]
  143. FumagalliF. CaffinoL. RacagniG. RivaM.A. Repeated stress prevents cocaine-induced activation of BDNF signaling in rat prefrontal cortex.Eur. Neuropsychopharmacol.200919640240810.1016/j.euroneuro.2009.01.003 19223270
     [Google Scholar]
  144. ArnstenA.F.T. Stress signalling pathways that impair prefrontal cortex structure and function.Nat. Rev. Neurosci.200910641042210.1038/nrn2648 19455173
     [Google Scholar]
  145. CaffinoL. RacagniG. FumagalliF. Stress and cocaine interact to modulate Arc/Arg3.1 expression in rat brain.Psychopharmacology 2011218124124810.1007/s00213‑011‑2331‑3 21590283
     [Google Scholar]
  146. FalkJ. FeingoldD. Environmental and cultural factors in the behavioral action of drugs. In: Psychopharmacology: The Third Generation of Progress. MeltzerH. New York, NYRaven Press198715031510
     [Google Scholar]
  147. BadianiA. BrowmanK.E. RobinsonT.E. Influence of novel versus home environments on sensitization to the psychomotor stimulant effects of cocaine and amphetamine.Brain Res.1995674229129810.1016/0006‑8993(95)00028‑O 7796109
     [Google Scholar]
  148. KlebaurJ.E. OstranderM.M. NortonC.S. WatsonS.J. AkilH. RobinsonT.E. The ability of amphetamine to evoke arc (Arg 3.1) mRNA expression in the caudate, nucleus accumbens and neocortex is modulated by environmental context.Brain Res.20029301-2303610.1016/S0006‑8993(01)03400‑X 11879792
     [Google Scholar]
  149. PenrodR.D. ThomsenM. TaniguchiM. GuoY. CowanC.W. SmithL.N. The activity-regulated cytoskeleton-associated protein, Arc/Arg3.1, influences mouse cocaine self-administration.Pharmacol. Biochem. Behav.202018817281810.1016/j.pbb.2019.172818 31682894
     [Google Scholar]
  150. FumagalliF. FranchiC. CaffinoL. RacagniG. RivaM.A. CervoL. Single session of cocaine intravenous self-administration shapes goal-oriented behaviours and up-regulates Arc mRNA levels in rat medial prefrontal cortex.Int. J. Neuropsychopharmacol.200912342342910.1017/S1461145708009681 19025723
     [Google Scholar]
  151. ZavalaA.R. OsredkarT. JoyceJ.N. NeisewanderJ.L. Upregulation of Arc mRNA expression in the prefrontal cortex following cue‐induced reinstatement of extinguished cocaine‐seeking behavior.Synapse200862642143110.1002/syn.20502 18361437
     [Google Scholar]
  152. SchiltzC.A. KelleyA.E. LandryC.F. Contextual cues associated with nicotine administration increase arc mRNA expression in corticolimbic areas of the rat brain.Eur. J. Neurosci.20052161703171110.1111/j.1460‑9568.2005.04001.x 15845097
     [Google Scholar]
  153. SchiltzC.A. BremerQ.Z. LandryC.F. KelleyA.E. Food-associated cues alter forebrain functional connectivity as assessed with immediate early gene and proenkephalin expression.BMC Biol.2007511610.1186/1741‑7007‑5‑16 17462082
     [Google Scholar]
  154. CaffinoL. GiannottiG. MalpighiC. RacagniG. FilipM. FumagalliF. Long-term abstinence from developmental cocaine exposure alters Arc/Arg3.1 modulation in the rat medial prefrontal cortex.Neurotox. Res.201426329930610.1007/s12640‑014‑9472‑1 24810662
     [Google Scholar]
  155. ContarinoA. KitchenerP. ValléeM. PapaleoF. PiazzaP.V. CRF1 receptor-deficiency increases cocaine reward.Neuropharmacology2017117414810.1016/j.neuropharm.2017.01.024 28137450
     [Google Scholar]
  156. ShiX. von WeltinE. FitzsimmonsE. DoC. Caban RiveraC. ChenC. Liu-ChenL.Y. UnterwaldE.M. Reactivation of cocaine contextual memory engages mechanistic target of rapamycin/S6 kinase 1 signaling.Front. Pharmacol.20221397693210.3389/fphar.2022.976932 36238569
     [Google Scholar]
  157. AlaghbandY. O’DellS.J. AzarniaS. KhalajA.J. GuzowskiJ.F. MarshallJ.F. Retrieval-induced NMDA receptor-dependent Arc expression in two models of cocaine-cue memory.Neurobiol. Learn. Mem.2014116798910.1016/j.nlm.2014.09.001 25225165
     [Google Scholar]
  158. ShepherdJ.D. BearM.F. New views of Arc, a master regulator of synaptic plasticity.Nat. Neurosci.201114327928410.1038/nn.2708 21278731
     [Google Scholar]
  159. GiannottiG. CaffinoL. CalabreseF. RacagniG. RivaM.A. FumagalliF. Prolonged abstinence from developmental cocaine exposure dysregulates BDNF and its signaling network in the medial prefrontal cortex of adult rats.Int. J. Neuropsychopharmacol.201417462563410.1017/S1461145713001454 24345425
     [Google Scholar]
  160. CalabreseF. RichettoJ. RacagniG. FeldonJ. MeyerU. RivaM.A. Effects of withdrawal from repeated amphetamine exposure in peri-puberty on neuroplasticity-related genes in mice.Neuroscience201325022223110.1016/j.neuroscience.2013.07.018 23872394
     [Google Scholar]
  161. GrimmJ.W. LuL. HayashiT. HopeB.T. SuT.P. ShahamY. Time-dependent increases in brain-derived neurotrophic factor protein levels within the mesolimbic dopamine system after withdrawal from cocaine: implications for incubation of cocaine craving.J. Neurosci.200323374274710.1523/JNEUROSCI.23‑03‑00742.2003 12574402
     [Google Scholar]
  162. GiannottiG. CanazzaI. CaffinoL. BilelS. OssatoA. FumagalliF. MartiM. The cathinones MDPV and α-PVP elicit different behavioral and molecular effects following acute exposure.Neurotox. Res.201732459460210.1007/s12640‑017‑9769‑y 28646469
     [Google Scholar]
  163. GainetdinovR.R. JonesS.R. FumagalliF. WightmanR.M. CaronM.G. Re-evaluation of the role of the dopamine transporter in dopamine system homeostasis1Published on the World Wide Web on 27 January 1998.1.Brain Res. Brain Res. Rev.1998262-314815310.1016/S0165‑0173(97)00063‑5 9651511
     [Google Scholar]
  164. BieverA. Boubaker-VitreJ. CutandoL. Gracia-RubioI. Costa-MattioliM. PuighermanalE. ValjentE. Repeated exposure to D-amphetamine decreases global protein synthesis and regulates the translation of a subset of mRNAs in the striatum.Front. Mol. Neurosci.2017916510.3389/fnmol.2016.00165 28119566
     [Google Scholar]
  165. BanerjeeP.S. AstonJ. KhundakarA.A. ZetterströmT.S.C. Differential regulation of psychostimulant‐induced gene expression of brain derived neurotrophic factor and the immediate‐early gene Arc in the juvenile and adult brain.Eur. J. Neurosci.200929346547610.1111/j.1460‑9568.2008.06601.x 19222557
     [Google Scholar]
  166. BenjaminG. JamesA. ClaireL. ZetterströmT. Age-dependent effects of methylphenidate in the prefrontal cortex: evidence from electrophysiological and Arc gene expression measurements.J. Psychopharmacol.201024121819182710.1177/0269881109359100 20142300
     [Google Scholar]
  167. ChaseT. CarreyN. SooE. WilkinsonM. Methylphenidate regulates activity regulated cytoskeletal associated but not brain-derived neurotrophic factor gene expression in the developing rat striatum.Neuroscience2007144396998410.1016/j.neuroscience.2006.10.035 17156936
     [Google Scholar]
  168. SchermaM. PalmasM.F. PisanuA. MasiaP. DedoniS. CamoglioC. FrattaW. CartaA.R. FaddaP. Induction of activity-regulated cytoskeleton-associated protein and c-fos expression in an animal model of anorexia nervosa.Nutrients20231517383010.3390/nu15173830 37686862
     [Google Scholar]
  169. AndreouC. BozikasV.P. The predictive significance of neurocognitive factors for functional outcome in bipolar disorder.Curr. Opin. Psychiatry2013261545910.1097/YCO.0b013e32835a2acf 23154642
     [Google Scholar]
  170. AddingtonJ. BarbatoM. The role of cognitive functioning in the outcome of those at clinical high risk for developing psychosis.Epidemiol. Psychiatr. Sci.201221433534210.1017/S204579601200042X 23174394
     [Google Scholar]
  171. ElizaldeN. PastorP.M. Garcia-GarcíaÁ.L. SerresF. VenzalaE. HuarteJ. RamírezM.J. Del RioJ. SharpT. TorderaR.M. Regulation of markers of synaptic function in mouse models of depression: chronic mild stress and decreased expression of VGLUT1.J. Neurochem.201011451302131410.1111/j.1471‑4159.2010.06854.x 20550627
     [Google Scholar]
  172. PinaudR. PennerM.R. RobertsonH.A. CurrieR.W. Upregulation of the immediate early gene arc in the brains of rats exposed to environmental enrichment: implications for molecular plasticity.Brain Res. Mol. Brain Res.2001911-2505610.1016/S0169‑328X(01)00121‑8 11457492
     [Google Scholar]
  173. VazdarjanovaA. McNaughtonB.L. BarnesC.A. WorleyP.F. GuzowskiJ.F. Experience-dependent coincident expression of the effector immediate-early genes arc and Homer 1a in hippocampal and neocortical neuronal networks.J. Neurosci.20022223100671007110.1523/JNEUROSCI.22‑23‑10067.2002 12451105
     [Google Scholar]
  174. PintoriN. PivaA. MottarliniF. DíazF.C. MaggiC. CaffinoL. FumagalliF. ChiamuleraC. Brief exposure to enriched environment rapidly shapes the glutamate synapses in the rat brain: A metaplastic fingerprint.Eur. J. Neurosci.202459598299510.1111/ejn.16279 38378276
     [Google Scholar]
  175. KozlovskyN. MatarM.A. KaplanZ. KotlerM. ZoharJ. CohenH. The immediate early gene Arc is associated with behavioral resilience to stress exposure in an animal model of posttraumatic stress disorder.Eur. Neuropsychopharmacol.200818210711610.1016/j.euroneuro.2007.04.009 17611082
     [Google Scholar]
/content/journals/cn/10.2174/011570159X338335240903075655
Loading
NeuropsychopharmARCology: Shaping Neuroplasticity through Arc/Arg3.1 Modulation
Curr. Neuropharmacol. 23, 650 (2025); https://doi.org/10.2174/011570159X338335240903075655
/content/journals/cn/10.2174/011570159X338335240903075655
/content/journals/cn/10.2174/011570159X338335240903075655
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): antidepressants; antipsychotics; Arc/Arg3.1; CNS disorders; immediate early genes; psychostimulants

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test