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Pharmacological NOS-1 Inhibition Within the Hippocampus Prevented Expression of Cocaine Sensitization: Correlation with Reduced Synaptic Transmission

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Abstract

Behavioral sensitization to psychostimulants hyperlocomotor effect is a useful model of addiction and craving. Particularly, cocaine sensitization in rats enhanced synaptic plasticity within the hippocampus, an important brain region for the associative learning processes underlying drug addiction. Nitric oxide (NO) is a neurotransmitter involved in both, hippocampal synaptic plasticity and cocaine sensitization. It has been previously demonstrated a key role of NOS-1/NO/sGC/cGMP signaling pathway in the development of cocaine sensitization and in the associated enhancement of hippocampal synaptic plasticity. The aim of the present investigation was to determine whether NOS-1 inhibition after development of cocaine sensitization was able to reverse it, and to characterize the involvement of the hippocampus in this phenomenon. Male Wistar rats were administered only with cocaine (15 mg/kg/day i.p.) for 5 days. Then, animals received 7-nitroindazole (NOS-1 inhibitor) either systemically for the next 5 days or a single intra-hippocampal administration. Development of sensitization and its expression after withdrawal were tested, as well as threshold for long-term potentiation in hippocampus, NOS-1, and CREB protein levels and gene expression. The results showed that NOS-1 protein levels and gene expression were increased only in sensitized animals as well as CREB gene expression. NOS-1 inhibition after sensitization reversed behavioral expression and the highest level of hippocampal synaptic plasticity. In conclusion, NO signaling within the hippocampus is critical for the development and expression of cocaine sensitization. Therefore, NOS-1 inhibition or NO signaling pathways interferences during short-term withdrawal after repeated cocaine administration may represent plausible pharmacological targets to prevent or reduce susceptibility to relapse.

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References

  1. Volkow N, Li TK (2005) The neuroscience of addiction. Nat Neurosci 8(11):1429–1430. https://doi.org/10.1038/nn1105-1429

    Article  CAS  PubMed  Google Scholar 

  2. Volkow ND, Wang GJ, Fowler JS, Tomasi D (2012) Addiction circuitry in the human brain. Annu Rev Pharmacol Toxicol 52:321–336. https://doi.org/10.1146/annurev-pharmtox-010611-134625

    Article  CAS  PubMed  Google Scholar 

  3. Stewart J (2000) Pathways to relapse: the neurobiology of drug- and stress-induced relapse to drug-taking. J Psychiatry Neurosci 25(2):125–136

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Fox HC, Seo D, Tuit K, Hansen J, Kimmerling A, Morgan PT, Sinha R (2012) Guanfacine effects on stress, drug craving and prefrontal activation in cocaine dependent individuals: preliminary findings. J Psychopharmacol 26(7):958–972. https://doi.org/10.1177/0269881111430746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. McKee SA, Potenza MN, Kober H, Sofuoglu M, Arnsten AF, Picciotto MR, Weinberger AH, Ashare R et al (2015) A translational investigation targeting stress-reactivity and prefrontal cognitive control with guanfacine for smoking cessation. J Psychopharmacol 29(3):300–311. https://doi.org/10.1177/0269881114562091

    Article  CAS  PubMed  Google Scholar 

  6. Moran-Santa Maria MM, Baker NL, Ramakrishnan V, Brady KT, McRae-Clark A (2015) Impact of acute guanfacine administration on stress and cue reactivity in cocaine-dependent individuals. Am J Dug Alcohol Abuse 41(2):146–152. https://doi.org/10.3109/00952990.2014.945590

    Article  Google Scholar 

  7. Pierce RC, Bell K, Duffy P, Kalivas PW (1996) Repeated cocaine augments excitatory amino acid transmission in the nucleus accumbens only in rats having developed behavioral sensitization. J Neurosci 16(4):1550–1560

    Article  CAS  Google Scholar 

  8. Boudreau AC, Wolf ME (2005) Behavioral sensitization to cocaine is associated with increased AMPA receptor surface expression in the nucleus accumbens. J Neurosci 25(40):9144–9151. https://doi.org/10.1523/jneurosci.2252-05.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Everitt BJ, Wolf ME (2002) Psychomotor stimulant addiction: a neural systems perspective. J Neurosci 22(9):3312–3320

    Article  CAS  Google Scholar 

  10. Robinson TE, Berridge KC (2000) The psychology and neurobiology of addiction: an incentive-sensitization view. Addiction 95(Suppl 2):S91–S117

    PubMed  Google Scholar 

  11. Nestler EJ (2002) Common molecular and cellular substrates of addiction and memory. Neurobiol Learn Mem 78(3):637–647. https://doi.org/10.1006/nlme.2002.4084

    Article  CAS  PubMed  Google Scholar 

  12. Wolf ME (2002) Addiction: making the connection between behavioral changes and neuronal plasticity in specific pathways. Mol Interv 2(3):146–157. https://doi.org/10.1124/mi.2.3.146

    Article  CAS  PubMed  Google Scholar 

  13. Robbins TW, Ersche KD, Everitt BJ (2008) Drug addiction and the memory systems of the brain. Ann N Y Acad Sci 1141:1–21. https://doi.org/10.1196/annals.1441.020

    Article  CAS  PubMed  Google Scholar 

  14. Sinha R (2001) How does stress increase risk of drug abuse and relapse? Psychopharmacology 158(4):343–359. https://doi.org/10.1007/s002130100917

    Article  CAS  PubMed  Google Scholar 

  15. Phillips RG, LeDoux JE (1992) Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav Neurosci 106(2):274–285

    Article  CAS  Google Scholar 

  16. Martin SJ, Grimwood PD, Morris RG (2000) Synaptic plasticity and memory: an evaluation of the hypothesis. Annu Rev Neurosci 23:649–711. https://doi.org/10.1146/annurev.neuro.23.1.649

    Article  CAS  PubMed  Google Scholar 

  17. Perez MF, Gabach LA, Almiron RS, Carlini VP, De Barioglio SR, Ramirez OA (2010) Different chronic cocaine administration protocols induce changes on dentate gyrus plasticity and hippocampal dependent behavior. Synapse 64(10):742–753. https://doi.org/10.1002/syn.20788

    Article  CAS  PubMed  Google Scholar 

  18. Thompson AM, Swant J, Gosnell BA, Wagner JJ (2004) Modulation of long-term potentiation in the rat hippocampus following cocaine self-administration. Neuroscience 127(1):177–185. https://doi.org/10.1016/j.neuroscience.2004.05.001

    Article  CAS  PubMed  Google Scholar 

  19. Vorel SR, Liu X, Hayes RJ, Spector JA, Gardner EL (2001) Relapse to cocaine-seeking after hippocampal theta burst stimulation. Science (New York, NY) 292(5519):1175–1178. https://doi.org/10.1126/science.1058043

    Article  CAS  Google Scholar 

  20. Conrad KL, Tseng KY, Uejima JL, Reimers JM, Heng LJ, Shaham Y, Marinelli M, Wolf ME (2008) Formation of accumbens GluR2-lacking AMPA receptors mediates incubation of cocaine craving. Nature 454(7200):118–121. https://doi.org/10.1038/nature06995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ma YY, Lee BR, Wang X, Guo C, Liu L, Cui R, Lan Y, Balcita-Pedicino JJ et al (2014) Bidirectional modulation of incubation of cocaine craving by silent synapse-based remodeling of prefrontal cortex to accumbens projections. Neuron 83(6):1453–1467. https://doi.org/10.1016/j.neuron.2014.08.023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Pascoli V, Terrier J, Espallergues J, Valjent E, O’Connor EC, Lüscher C (2014) Contrasting forms of cocaine-evoked plasticity control components of relapse. Nature 509:459–464. https://doi.org/10.1038/nature13257

    Article  CAS  PubMed  Google Scholar 

  23. Grant S, London ED, Newlin DB, Villemagne VL, Liu X, Contoreggi C, Phillips RL, Kimes AS et al (1996) Activation of memory circuits during cue-elicited cocaine craving. Proc Natl Acad Sci U S A 93(21):12040–12045

    Article  CAS  Google Scholar 

  24. Kilts CD, Schweitzer JB, Quinn CK, Gross RE, Faber TL, Muhammad F, Ely TD, Hoffman JM et al (2001) Neural activity related to drug craving in cocaine addiction. Arch Gen Psychiatry 58(4):334–341

    Article  CAS  Google Scholar 

  25. Wexler BE, Gottschalk CH, Fulbright RK, Prohovnik I, Lacadie CM, Rounsaville BJ, Gore JC (2001) Functional magnetic resonance imaging of cocaine craving. Am J Psychiatry 158(1):86–95. https://doi.org/10.1176/appi.ajp.158.1.86

    Article  CAS  PubMed  Google Scholar 

  26. Chase HW, Eickhoff SB, Laird AR, Hogarth L (2011) The neural basis of drug stimulus processing and craving: an activation likelihood estimation meta-analysis. Biol Psychiatry 70(8):785–793. https://doi.org/10.1016/j.biopsych.2011.05.025

    Article  PubMed  PubMed Central  Google Scholar 

  27. Tang DW, Fellows LK, Small DM, Dagher A (2012) Food and drug cues activate similar brain regions: a meta-analysis of functional MRI studies. Physiol Behav 106(3):317–324. https://doi.org/10.1016/j.physbeh.2012.03.009

    Article  CAS  PubMed  Google Scholar 

  28. Fotros A, Casey KF, Larcher K, Verhaeghe JA, Cox SM, Gravel P, Reader AJ, Dagher A et al (2013) Cocaine cue-induced dopamine release in amygdala and hippocampus: a high-resolution PET [(1)(8)F] fallypride study in cocaine dependent participants. Neuropsychopharmacology 38(9):1780–1788. https://doi.org/10.1038/npp.2013.77

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hitchcock LN, Lattal KM (2018) Involvement of the dorsal hippocampus in expression and extinction of cocaine-induced conditioned place preference. Hippocampus 28(3):226–238. https://doi.org/10.1002/hipo.22826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wittmann BC, Schott BH, Guderian S, Frey JU, Heinze HJ, Duzel E (2005) Reward-related FMRI activation of dopaminergic midbrain is associated with enhanced hippocampus-dependent long-term memory formation. Neuron 45(3):459–467. https://doi.org/10.1016/j.neuron.2005.01.010

    Article  CAS  PubMed  Google Scholar 

  31. Adcock RA, Thangavel A, Whitfield-Gabrieli S, Knutson B, Gabrieli JD (2006) Reward-motivated learning: mesolimbic activation precedes memory formation. Neuron 50(3):507–517. https://doi.org/10.1016/j.neuron.2006.03.036

    Article  CAS  PubMed  Google Scholar 

  32. Berke JD, Hyman SE (2000) Addiction, dopamine, and the molecular mechanisms of memory. Neuron 25(3):515–532

    Article  CAS  Google Scholar 

  33. Hyman SE, Malenka RC (2001) Addiction and the brain: the neurobiology of compulsion and its persistence. Nat Rev Neurosci 2(10):695–703. https://doi.org/10.1038/35094560

    Article  CAS  PubMed  Google Scholar 

  34. Brami-Cherrier K, Valjent E, Herve D, Darragh J, Corvol JC, Pages C, Arthur SJ, Girault JA et al (2005) Parsing molecular and behavioral effects of cocaine in mitogen- and stress-activated protein kinase-1-deficient mice. J Neurosci 25(49):11444–11454. https://doi.org/10.1523/jneurosci.1711-05.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kuo YM, Liang KC, Chen HH, Cherng CG, Lee HT, Lin Y, Huang AM, Liao RM et al (2007) Cocaine-but not methamphetamine-associated memory requires de novo protein synthesis. Neurobiol Learn Mem 87(1):93–100. https://doi.org/10.1016/j.nlm.2006.06.004

    Article  CAS  PubMed  Google Scholar 

  36. Madsen HB, Brown RM, Lawrence AJ (2012) Neuroplasticity in addiction: cellular and transcriptional perspectives. Front Mol Neurosci 5:99. https://doi.org/10.3389/fnmol.2012.00099

    Article  PubMed  PubMed Central  Google Scholar 

  37. Buenrostro-Jauregui M, Ciudad-Roberts A, Moreno J, Munoz-Villegas P, Lopez-Arnau R, Pubill D, Escubedo E, Camarasa J (2016) Changes in CREB and deltaFosB are associated with the behavioural sensitization induced by methylenedioxypyrovalerone. J Psychopharmacol 30(7):707–712. https://doi.org/10.1177/0269881116645300

    Article  CAS  PubMed  Google Scholar 

  38. Valzachi MC, Teodorov E, Marcourakis T, Bailey A, Camarini R (2013) Enhancement of behavioral sensitization, anxiety-like behavior, and hippocampal and frontal cortical CREB levels following cocaine abstinence in mice exposed to cocaine during adolescence. PLoS One 8(10):e78317. https://doi.org/10.1371/journal.pone.0078317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Barco A, Lopez de Armentia M, Alarcon JM (2008) Synapse-specific stabilization of plasticity processes: the synaptic tagging and capture hypothesis revisited 10 years later. Neurosci Biobehav Rev 32(4):831–851. https://doi.org/10.1016/j.neubiorev.2008.01.002

    Article  PubMed  Google Scholar 

  40. Mustafa AK, Gadalla MM, Snyder SH (2009) Signaling by gasotransmitters. Sci Signal 2(68):re2. https://doi.org/10.1126/scisignal.268re2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Garthwaite J (2010) New insight into the functioning of nitric oxide-receptive guanylyl cyclase: physiological and pharmacological implications. Mol Cell Biochem 334(1–2):221–232. https://doi.org/10.1007/s11010-009-0318-8

    Article  CAS  PubMed  Google Scholar 

  42. Garthwaite J (2008) Concepts of neural nitric oxide-mediated transmission. Eur J Neurosci 27(11):2783–2802. https://doi.org/10.1111/j.1460-9568.2008.06285.x

    Article  PubMed  PubMed Central  Google Scholar 

  43. Prast H, Philippu A (2001) Nitric oxide as modulator of neuronal function. Prog Neurobiol 64(1):51–68

    Article  CAS  Google Scholar 

  44. Itzhak Y (1996) Attenuation of cocaine kindling by 7-nitroindazole, an inhibitor of brain nitric oxide synthase. Neuropharmacology 35(8):1065–1073

    Article  CAS  Google Scholar 

  45. Kim HS, Park WK (1995) Nitric oxide mediation of cocaine-induced dopaminergic behaviors: ambulation-accelerating activity, reverse tolerance and conditioned place preference in mice. J Pharmacol Exp Ther 275(2):551–557

    CAS  PubMed  Google Scholar 

  46. Itzhak Y, Ali SF, Martin JL, Black MD, Huang PL (1998) Resistance of neuronal nitric oxide synthase-deficient mice to cocaine-induced locomotor sensitization. Psychopharmacology 140(3):378–386

    Article  CAS  Google Scholar 

  47. Itzhak Y, Roger-Sanchez C, Kelley JB, Anderson KL (2010) Discrimination between cocaine-associated context and cue in a modified conditioned place preference paradigm: role of the nNOS gene in cue conditioning. Int J Neuropsychopharmacol 13(2):171–180. https://doi.org/10.1017/s1461145709990666

    Article  CAS  PubMed  Google Scholar 

  48. Orsini C, Izzo E, Koob GF, Pulvirenti L (2002) Blockade of nitric oxide synthesis reduces responding for cocaine self-administration during extinction and reinstatement. Brain Res 925(2):133–140

    Article  CAS  Google Scholar 

  49. Nasif FJ, Hu XT, Ramirez OA, Perez MF (2011) Inhibition of neuronal nitric oxide synthase prevents alterations in medial prefrontal cortex excitability induced by repeated cocaine administration. Psychopharmacology 218(2):323–330. https://doi.org/10.1007/s00213-010-2105-3

    Article  CAS  PubMed  Google Scholar 

  50. Selvakumar B, Campbell PW, Milovanovic M, Park DJ, West AR, Snyder SH, Wolf ME (2014) AMPA receptor upregulation in the nucleus accumbens shell of cocaine-sensitized rats depends upon S-nitrosylation of stargazin. Neuropharmacology 77:28–38. https://doi.org/10.1016/j.neuropharm.2013.08.036

    Article  CAS  PubMed  Google Scholar 

  51. Gabach LA, Carlini VP, Monti MC, Maglio LE, De Barioglio SR, Perez MF (2013) Involvement of nNOS/NO/sGC/cGMP signaling pathway in cocaine sensitization and in the associated hippocampal alterations: does phosphodiesterase 5 inhibition help to drug vulnerability? Psychopharmacology 229(1):41–50. https://doi.org/10.1007/s00213-013-3084-y

    Article  CAS  PubMed  Google Scholar 

  52. Badanich KA, Adler KJ, Kirstein CL (2006) Adolescents differ from adults in cocaine conditioned place preference and cocaine-induced dopamine in the nucleus accumbens septi. Eur J Pharmacol 550(1–3):95–106. https://doi.org/10.1016/j.ejphar.2006.08.034

    Article  CAS  PubMed  Google Scholar 

  53. Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates: hard cover edition, 6th edn. Academic, Cambridge

    Google Scholar 

  54. Teyler TJ, DiScenna P (1987) Long-term potentiation. Annu Rev Neurosci 10:131–161. https://doi.org/10.1146/annurev.ne.10.030187.001023

    Article  CAS  PubMed  Google Scholar 

  55. Poretti MB, Rask-Andersen M, Kumar P, Rubiales de Barioglio S, Fiol de Cuneo M, Schioth HB, Carlini VP (2015) Ghrelin effects expression of several genes associated with depression-like behavior. Prog Neuro-Psychopharmacol Biol Psychiatry 56:227–234. https://doi.org/10.1016/j.pnpbp.2014.09.012

    Article  CAS  Google Scholar 

  56. Itzhak Y (1997) Modulation of cocaine- and methamphetamine-induced behavioral sensitization by inhibition of brain nitric oxide synthase. J Pharmacol Exp Ther 282(2):521–527

    CAS  PubMed  Google Scholar 

  57. Lisman JE, Grace AA (2005) The hippocampal-VTA loop: controlling the entry of information into long-term memory. Neuron 46(5):703–713. https://doi.org/10.1016/j.neuron.2005.05.002

    Article  CAS  PubMed  Google Scholar 

  58. Scoville WB, Milner B (1957) Loss of recent memory after bilateral hippocampal lesions. J Neurol Neurosurg Psychiatry 20(1):11–21. https://doi.org/10.1136/jnnp.20.1.11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Hernández-Rabaza V, Hontecillas-Prieto L, Velázquez-Sánchez C, Ferragud A, Pérez-Villaba A, Arcusa A, Barcia JA, Trejo JL et al (2008) The hippocampal dentate gyrus is essential for generating contextual memories of fear and drug-induced reward. Neurobiol Learn Mem 90(3):553–559. https://doi.org/10.1016/j.nlm.2008.06.008

    Article  CAS  PubMed  Google Scholar 

  60. Ntamati NR, Lüscher C (2016) VTA projection neurons releasing GABA and glutamate in the dentate gyrus. eNeuro 3(4). https://doi.org/10.1523/eneuro.0137-16.2016

    Article  Google Scholar 

  61. Ramirez DR, Bell GH, Lasseter HC, Xie X, Traina SA, Fuchs RA (2009) Dorsal hippocampal regulation of memory reconsolidation processes that facilitate drug context-induced cocaine-seeking behavior in rats. Eur J Neurosci 30(5):901–912. https://doi.org/10.1111/j.1460-9568.2009.06889.x

    Article  PubMed  PubMed Central  Google Scholar 

  62. Dong Y, Nasif FJ, Tsui JJ, Ju WY, Cooper DC, Hu XT, Malenka RC, White FJ (2005) Cocaine-induced plasticity of intrinsic membrane properties in prefrontal cortex pyramidal neurons: adaptations in potassium currents. J Neurosci 25(4):936–940. https://doi.org/10.1523/jneurosci.4715-04.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Nasif FJ, Hu XT, White FJ (2005) Repeated cocaine administration increases voltage-sensitive calcium currents in response to membrane depolarization in medial prefrontal cortex pyramidal neurons. J Neurosci 25(14):3674–3679. https://doi.org/10.1523/jneurosci.0010-05.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Nasif FJ, Sidiropoulou K, Hu XT, White FJ (2005) Repeated cocaine administration increases membrane excitability of pyramidal neurons in the rat medial prefrontal cortex. J Pharmacol Exp Ther 312(3):1305–1313. https://doi.org/10.1124/jpet.104.075184

    Article  CAS  PubMed  Google Scholar 

  65. Brenman JE, Xia H, Chao DS, Black SM, Bredt DS (1997) Regulation of neuronal nitric oxide synthase through alternative transcripts. Dev Neurosci 19(3):224–231. https://doi.org/10.1159/000111211

    Article  CAS  PubMed  Google Scholar 

  66. Ogura T, Yokoyama T, Fujisawa H, Kurashima Y, Esumi H (1993) Structural diversity of neuronal nitric oxide synthase mRNA in the nervous system. Biochem Biophys Res Commun 193(3):1014–1022. https://doi.org/10.1006/bbrc.1993.1726

    Article  CAS  PubMed  Google Scholar 

  67. Silvagno F, Xia H, Bredt DS (1996) Neuronal nitric-oxide synthase-mu, an alternatively spliced isoform expressed in differentiated skeletal muscle. J Biol Chem 271(19):11204–11208. https://doi.org/10.1074/jbc.271.19.11204

    Article  CAS  PubMed  Google Scholar 

  68. Wang Y, Newton DC, Robb GB, Kau CL, Miller TL, Cheung AH, Hall AV, VanDamme S et al (1999) RNA diversity has profound effects on the translation of neuronal nitric oxide synthase. Proc Natl Acad Sci U S A 96(21):12150–12155. https://doi.org/10.1073/pnas.96.21.12150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Huang PL, Dawson TM, Bredt DS, Snyder SH, Fishman MC (1993) Targeted disruption of the neuronal nitric oxide synthase gene. Cell 75(7):1273–1286. https://doi.org/10.1016/0092-8674(93)90615-w

    Article  CAS  PubMed  Google Scholar 

  70. Garthwaite J, Boulton CL (1995) Nitric oxide signaling in the central nervous system. Annu Rev Physiol 57:683–706. https://doi.org/10.1146/annurev.ph.57.030195.003343

    Article  CAS  PubMed  Google Scholar 

  71. Engelhardt T, Lowe PR, Galley HF, Webster NR (2006) Inhibition of neuronal nitric oxide synthase reduces isoflurane MAC and motor activity even in nNOS knockout mice. Br J Anaesth 96(3):361–366. https://doi.org/10.1093/bja/ael010

    Article  CAS  PubMed  Google Scholar 

  72. Baranano DE, Snyder SH (2001) Neural roles for heme oxygenase: contrasts to nitric oxide synthase. Proc Natl Acad Sci U S A 98(20):10996–11002. https://doi.org/10.1073/pnas.191351298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Itzhak Y, Anderson KL (2008) Ethanol-induced behavioral sensitization in adolescent and adult mice: role of the nNOS gene. Alcohol Clin Exp Res 32(10):1839–1848. https://doi.org/10.1111/j.1530-0277.2008.00766.x

    Article  CAS  PubMed  Google Scholar 

  74. Itzhak Y, Roger-Sanchez C, Anderson KL (2009) Role of the nNOS gene in ethanol-induced conditioned place preference in mice. Alcohol (Fayetteville, NY) 43(4):285–291. https://doi.org/10.1016/j.alcohol.2009.02.004

    Article  CAS  Google Scholar 

  75. Park K, Vora U, Darling SF, Kolta MG, Soliman KF (2001) The role of inducible nitric oxide synthase in cocaine-induced locomotor sensitization. Physiol Behav 74(4–5):441–447. https://doi.org/10.1016/s0031-9384(01)00588-1

    Article  CAS  PubMed  Google Scholar 

  76. Reid MS, Berger SP (1996) Evidence for sensitization of cocaine-induced nucleus accumbens glutamate release. Neuroreport 7(7):1325–1329

    Article  CAS  Google Scholar 

  77. Smith JA, Mo Q, Guo H, Kunko PM, Robinson SE (1995) Cocaine increases extraneuronal levels of aspartate and glutamate in the nucleus accumbens. Brain Res 683(2):264–269. https://doi.org/10.1016/0006-8993(95)00383-2

    Article  CAS  PubMed  Google Scholar 

  78. Hewett SJ, Csernansky CA, Choi DW (1994) Selective potentiation of NMDA-induced neuronal injury following induction of astrocytic iNOS. Neuron 13(2):487–494

    Article  CAS  Google Scholar 

  79. Farmer J, Zhao X, van Praag H, Wodtke K, Gage FH, Christie BR (2004) Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-Dawley rats in vivo. Neuroscience 124(1):71–79. https://doi.org/10.1016/j.neuroscience.2003.09.029

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors are grateful to Technicians Estela Salde and Lorena Mercado for their laboratory technical assistance with the behavioral and molecular biology experiments, and to Dr. Fernando J. Nasif for his helpful comments on the manuscript.

Funding

This work was supported in Argentina by grants from Secretaría de Ciencia y Tecnología de la Universidad Nacional de Córdoba (SECyT-UNC) and Agencia Nacional de Promoción Científica y Tecnológica (PICT 2017-2426) to Dr. Perez and in Sweden by grants from the Swedish Research Foundation (VR) and the Swedish Brain Research Foundation to Dr. Schiöth.

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  1. Facultad de Ciencias Químicas, Departamento de Farmacología, IFEC-CONICET, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, 5000, Córdoba, Argentina

    Emilce Artur de la Villarmois, Laura A. Gabach, Victoria Occhieppo & Mariela Fernanda Pérez

  2. Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden

    Santiago Bianconi, Maria Belen Poretti, Helgi B. Schiöth & Valeria P. Carlini

  3. INICSA-CONICET, Instituto de Fisiología, Facultad de Ciencias Médicas, UNC, Córdoba, Argentina

    Santiago Bianconi, Maria Belen Poretti & Valeria P. Carlini

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  1. Emilce Artur de la Villarmois
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  2. Laura A. Gabach
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  3. Santiago Bianconi
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  8. Mariela Fernanda Pérez
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Contributions

MFP, LAG, and EA were responsible for the study concept and design. LAG, EA, and VO contributed to the acquisition of animal data. SB, MBP, HBS, and VPC performed the gene expression experiments and analysis. LAG and EA performed western blot and electrophysiological experiments and analysis. MFP and EA drafted the manuscript. All authors critically reviewed content and approved final version for publication.

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Correspondence to Mariela Fernanda Pérez.

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All procedures were carried out in accordance with the Guide for the Care and Use of Laboratory Animals as adopted and promulgated by the National Institutes of Health and the EU (Eighth Edition, 2011) and approved by the Animal Care and Use Committee, School of Chemical Sciences (Res. HCD 48/2014), National University of Cordoba. Experiments were made minimizing the number of animals used and their suffering.

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Artur de la Villarmois, E., Gabach, L.A., Bianconi, S. et al. Pharmacological NOS-1 Inhibition Within the Hippocampus Prevented Expression of Cocaine Sensitization: Correlation with Reduced Synaptic Transmission. Mol Neurobiol 57, 450–460 (2020). https://doi.org/10.1007/s12035-019-01725-3

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