Skip to main content

Advertisement

SpringerLink
Log in

∆9-Tetrahydrocannabinol Decreases NOP Receptor Density and mRNA Levels in Human SH-SY5Y Cells

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Several studies demonstrated a cross-talk between the opioid and cannabinoid system. The NOP receptor and its endogenous ligand nociceptin/orphanin FQ represent an opioid-related functional entity that mediates some non-classical opioid effects. The relationship between cannabinoid and nociceptin/NOP system is yet poorly explored. In this study, we used the neuroblastoma SH-SY5Y cell line to investigate the effect of delta-9-tetrahydrocannabinol (∆9-THC) on nociceptin/NOP system. Results revealed that the exposure to ∆9-THC (100, 150, and 200 nM) for 24 h produces a dose-dependent NOP receptor B max down-regulation. Moreover, ∆9-THC caused a dose-dependent decrease in NOP mRNA levels. The selective cannabinoid receptor CB1 antagonist AM251 (1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide) reduces both effects, suggesting that ∆9-THC activation of CB1 receptor is involved in the observed effects. These data show evidence of a cross-talk between NOP and CB1 receptors, thus suggesting a possible interplay between cannabinoid and nociceptin/NOP system.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Azizi P, Haghparast A, Hassanpour-Ezatti M (2009) Effects of CB1 receptor antagonist within the nucleus accumbens on the acquisition and expression of morphine-induced conditioned place preference in morphine-sensitized rats. Behav Brain Res 197:119–124

    Article  PubMed  CAS  Google Scholar 

  • Calò G, Rizzi A, Bigoni R, Guerrini R, Salvadori S, Regoli D (2002) Pharmacological profile of nociceptin/orphanin FQ receptors. Clin Exp Pharmacol Physiol 29:223–228

    Article  PubMed  Google Scholar 

  • Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159

    Article  PubMed  CAS  Google Scholar 

  • Ciccocioppo R, Panocka I, Polidori C, Regoli D, Massi M (1999) Effect of nociceptin on alcohol intake in alcohol-preferring rats. Psychopharmacol Berl 141:220–224

    Article  CAS  Google Scholar 

  • Ciccocioppo R, Angeletti S, Panocka I, Massi M (2000) Nociceptin/orphanin FQ and drugs of abuse. Peptides 21:1071–1080

    Article  PubMed  CAS  Google Scholar 

  • Cichewicz DL (2004) Synergistic interactions between cannabinoid and opioid analgesics. Life Sci 74:1317–1324

    Article  PubMed  CAS  Google Scholar 

  • Cichewicz DL, Martin ZL, Smith FL, Welch SP (1999) Enhancement mu opioid antinociception by oral delta9-tetrahydrocannabinol: dose response analysis and receptor identification. J Pharmacol Exp Ther 289:859–867

    PubMed  CAS  Google Scholar 

  • Cichewicz DL, Haller VL, Welch SP (2001) Changes in opioid and cannabinoid receptor protein following short-term combination treatment with delta(9)-tetrahydrocannabinol and morphine. J Pharmacol Exp Ther 297:121–127

    PubMed  CAS  Google Scholar 

  • Connor M, Yeo A, Henderson G (1996) The effect of nociceptin on Ca2+ channel current and intracellular Ca2+ in SH-SY5Y human neuroblastoma cell line. Br J Pharmacol 118:205–207

    PubMed  CAS  Google Scholar 

  • Corchero J, Avila MA, Fuentes JA, Manzanares J (1997a) Delta-9-Tetrahydrocannabinol increases prodynorphin and proenkephalin gene expression in the spinal cord of the rat. Life Sci 61:39–43

    Article  Google Scholar 

  • Corchero J, Fuentes JA, Manzanares J (1997b) Delta 9-Tetrahydrocannabinol increases proopiomelanocortin gene expression in the arcuate nucleus of the rat hypothalamus. Eur J Pharmacol 323:193–195

    Article  PubMed  CAS  Google Scholar 

  • Cox BM, Chavkin C, Christie MJ et al (2000) Opioid receptors. In: Girdlestone D (ed) The IUPHAR compendium of receptor characterization and classification. IUPHAR Media, London, pp 321–333

    Google Scholar 

  • Darland T, Heinricher MM, Grandy DK (1998) Orphanin FQ/nociceptin: a role in pain, and analgesia, but so much more. Trends Neurosci 21:215–221

    Article  PubMed  CAS  Google Scholar 

  • Di Giannuario A, Pieretti S, Catalani A, Loizzo A (1999) Orphanin FQ reduces morphine-induced dopamine release in the nucleus accumbens: a microdialysis study in rats. Neurosci Lett 272:183–186

    Article  PubMed  Google Scholar 

  • Foord SM, Bonner TI, Neubig RR et al (2005) International Union of Pharmacology XLVI. G protein-coupled receptor list. Pharmacol Rev 57:279–288

    Article  PubMed  CAS  Google Scholar 

  • Gardner EL (2005) Endocannabinoid signaling system and brain reward: emphasis on dopamine. Pharmacol Biochem Behav 81:263–284

    Article  PubMed  CAS  Google Scholar 

  • Hawes BE, Graziano MP, Lambert DG (2000) Cellular actions of nociceptin: transduction mechanisms. Peptides 21:961–967

    Article  PubMed  CAS  Google Scholar 

  • Heinricher MM, McGaraughty S, Grandy DK (1997) Circuitry underlying antiopioid actions of orphanin FQ in the rostral ventromedial medulla. J Neurophysiol 78:3351–3358

    PubMed  CAS  Google Scholar 

  • Henderson G, McKnight AT (1997) The orphan opioid receptor and its endogenous ligand nociceptin/orphanin FQ. Trends Pharmacol Sci 18:293–300

    Article  PubMed  CAS  Google Scholar 

  • Hojo M, Sudo Y, Ando Y et al (2008) Mu-Opioid receptor forms a functional heterodimer with cannabinoid CB1 receptor: electrophysiological and FRET assay analysis. J Pharmacol Sci 108:308–319

    Article  PubMed  CAS  Google Scholar 

  • Howlett AC, Barth F, Bonner TI et al (2002) International Union of Pharmacology XXVII. Classification of cannabinoid receptors. Pharmacol Rev 54:161–202

    Article  PubMed  CAS  Google Scholar 

  • Ikeda K, Watanabe M, Ichikawa TT, Kobayashi T, Yano R, Kumanishi T (1998) Distribution of prepronociceptin/orphanin FQ mRNA and its receptor mRNA in developing and adult mouse central nervous systems. J Comp Neurol 399:139–151

    Article  PubMed  CAS  Google Scholar 

  • Jenck F, Moreau JL, Martin JR et al (1997) Orphanin FQ acts as an anxiolytic to attenuate behavioral responses to stress. Proc Natl Acad Sci USA 94:14854–14858

    Article  PubMed  CAS  Google Scholar 

  • Klegeris A, Bissonnette CJ, McGeer PL (2003) Reduction of human monocytic cell neurotoxicity and cytokine secretion by ligands of the cannabinoid-type CB2 receptor. Br J Pharmacol 139:775–786

    Article  PubMed  CAS  Google Scholar 

  • Kotlinska J, Wichmann J, Legowska A, Rolka K, Silberring J (2002) Orphanin FQ/nociceptin but not Ro 65–6570 inhibits the expression of cocaine-induced conditioned place preference. Behav Pharmacol 13:229–235

    Article  PubMed  CAS  Google Scholar 

  • Kotlinska J, Rafalski P, Biala G, Dylag T, Rolka K, Silberring J (2003) Nociceptin inhibits acquisition of amphetamine-induced place preference and sensitization to stereotypy in rats. Eur J Pharmacol 474:233–239

    Article  PubMed  CAS  Google Scholar 

  • Lambert DG (2008) The nociceptin/orphanin FQ receptor: a target with broad therapeutic potential. Nat Rev Drug Discov 7:694–710

    Article  PubMed  CAS  Google Scholar 

  • López-Moreno JA, López-Jiménez A, Gorriti MA, de Fonseca FR (2010) Functional interactions between endogenous cannabinoid and opioid systems: focus on alcohol, genetics and drug-addicted behaviors. Curr Drug Targets 11:406–428

    Article  PubMed  Google Scholar 

  • Luk T, Jin W, Zvonok A, Lu D, Lin XZ, Chavkin C, Makriyannis A, Mackie K (2004) Identification of a potent and highly efficacious, yet slowly desensitizing CB1 cannabinoid receptor agonist. Br J Pharmacol 142:495–500

    Article  PubMed  CAS  Google Scholar 

  • Lutfy K, Do T, Maidment NT (2001) Orphanin FQ/nociceptin attenuates motor stimulation and changes in nucleus accumbens extracellular dopamine induced by cocaine in rats. Psychopharmacol Berl 154:1–7

    Article  CAS  Google Scholar 

  • Manabe T, Noda Y, Mamiya T et al (1998) Facilitation of long-term potentiation and memory in mice lacking nociceptin receptors. Nature 394:577–581

    Article  PubMed  CAS  Google Scholar 

  • Manzanedo C, Aguilar MA, Rodríguez-Arias M, Navarro M, Miñarro J (2004) Cannabinoid agonist-induced sensitisation to morphine place preference in mice. Neuroreport 15:1373–1377

    Article  PubMed  CAS  Google Scholar 

  • Mason DJ Jr, Lowe J, Welch SP (1999) Cannabinoid modulation of dynorphin A: correlation to cannabinoid-induced antinociception. Eur J Pharmacol 378:237–248

    Article  PubMed  CAS  Google Scholar 

  • Mechoulam R, Gaoni Y (1967) The absolute configuration of delta-1-tetrahydrocannabinol, the major active constituent of hashish. Tetra Lett 12:1109–1111

    Article  CAS  Google Scholar 

  • Meunier JC, Mollereau C, Toll L et al (1995) Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor. Nature 377:532–535

    Article  PubMed  CAS  Google Scholar 

  • Mogil JS, Grisel JE, Reinscheid RK, Civelli O, Belknap JK, Grandy DK (1996) Orphanin FQ is a functional anti-opioid peptide. Neuroscience 75:333–337

    Article  PubMed  CAS  Google Scholar 

  • Mollereau C, Parmentier M, Mailleux P et al (1994) ORL1, a novel member of the opioid receptor family. Cloning, functional expression and localization. FEBS Lett 341:33–38

    Article  PubMed  CAS  Google Scholar 

  • Mossmann T (1993) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assay. J Iimmunol Meth 65:55–63

    Article  Google Scholar 

  • Motulsky HJ (1999) Analyzing data with GraphPad Prism. GraphPad Software Inc., San Diego

    Google Scholar 

  • Murphy NP, Ly HT, Maidment NT (1996) Intracerebroventricular orphanin FQ/nociceptin suppresses dopamine release in the nucleus accumbens of anaesthetized rats. Neuroscience 75:1–4

    Article  PubMed  CAS  Google Scholar 

  • Navarro M, Carrera MR, Fratta W et al (2001) Functional interaction between opioid and cannabinoid receptors in drug self-administration. J Neurosci 21:5344–5350

    PubMed  CAS  Google Scholar 

  • Pan Z, Hirakawa N, Fields HL (2000) A cellular mechanism for the bidirectional pain-modulating actions of orphanin FQ/nociceptin. Neuron 26:515–522

    Article  PubMed  CAS  Google Scholar 

  • Parolaro D, Viganò T, Rubino T (2005) Endocannabinoids and drug dependence. Curr Drug Targets CNS Neurol Disord 4:643–655

    Article  PubMed  CAS  Google Scholar 

  • Parolaro D, Rubino T, Viganò D, Massi P, Guidali C, Realini N (2010) Cellular mechanisms underlying the interaction between cannabinoid and opioid system. Curr Drug Targets 11:393–405

    Article  PubMed  CAS  Google Scholar 

  • Pertwee RG (2008) The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: D9-tetrahydrocannabinol, cannabidiol and D9-tetrahydrocannabivarin. Br J Pharmacol 153:199–215

    Article  PubMed  CAS  Google Scholar 

  • Pietras TA, Rowland NE (2002) Effect of opioid and cannabinoid receptor antagonism on orphanin FQ-induced hyperphagia in rats. Eur J Pharmacol 442:237–439

    Article  PubMed  CAS  Google Scholar 

  • Pomonis JD, Billington CJ, Levine AS (1996) Orphanin FQ, agonist of orphan opioid receptor ORL1, stimulates feeding in rats. Neuro Rep 8:369–371

    CAS  Google Scholar 

  • Rawls SM, Schroeder JA, Ding Z, Rodriguez T, Zaveri N (2007) NOP receptor antagonist, JTC-801, blocks cannabinoid-evoked hypothermia in rats. Neuropep 41:239–247

    Article  CAS  Google Scholar 

  • Rawls SM, Cabassa J, Geller EB, Adler MW (2002) CB1 receptors in the preoptic anterior hypothalamus regulate WIN 55212–2 [(4,5-dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphthalenyl-carbonyl)-6H-pyrrolo[3,2,1ij]quinolin-6-one]-induced hypothermia. J Pharmacol Exp Ther 301:963–968

    Article  PubMed  CAS  Google Scholar 

  • Reinscheid RK, Nothacker HP, Bourson A et al (1995) Orphanin FQ: a neuropeptide that activates an opioid-like G protein-coupled receptor. Science 270:792–794

    Article  PubMed  CAS  Google Scholar 

  • Rios C, Gomes I, Devi LA (2006) Mu opioid and CB1 cannabinoid receptor interactions: reciprocal inhibition of receptor signaling and neuritogenesis. Br J Pharmacol 148:387–395

    Article  PubMed  CAS  Google Scholar 

  • Sakoori K, Murphy NP (2004) Central administration of nociceptin/orphanin FQ blocks the acquisition of conditioned place preference to morphine and cocaine, but not conditioned place aversion to naloxone in mice. Psychopharmacol Berl 172:129–136

    Article  CAS  Google Scholar 

  • Sandin J, Georgieva J, Schött PA, Ogren SO, Terenius L (1997) Nociceptin/orphanin FQ microinjected into hippocampus impairs spatial learning in rats. Eur J Neurosci 9:194–197

    Article  PubMed  CAS  Google Scholar 

  • Schoffelmeer AN, Hogenboom F, Wardeh G, De Vries TJ (2006) Interactions between CB1 cannabinoid and mu opioid receptors mediating inhibition of neurotransmitter release in rat nucleus accumbens core. Neuropharmacology 51:773–781

    Article  PubMed  CAS  Google Scholar 

  • Sperlágh B, Windisch K, Andó RD, Sylvester VE (2009) Neurochemical evidence that stimulation of CB1 cannabinoid receptors on GABAergic nerve terminals activates the dopaminergic reward system by increasing dopamine release in the rat nucleus accumbens. Neurochem Int 54:452–457

    Article  PubMed  Google Scholar 

  • Yakimova KS, Pierau FK (1999) Nociceptin/orphanin FQ: effects on thermoregulation in rats. Meth Find Exp Clin Pharmacol 21:345–352

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by grants from the Italian Ministry for the University and Scientific Research (PRIN 2008, RFO 2009).

Author information

Authors and Affiliations

  1. Department of Pharmacology, University of Bologna, Via Irnerio 48, Bologna, 40126, Italy

    Rosalia Cannarsa, Donatella Carretta, Francesca Lattanzio, Sanzio Candeletti & Patrizia Romualdi

Authors
  1. Rosalia Cannarsa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Donatella Carretta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Francesca Lattanzio
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sanzio Candeletti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Patrizia Romualdi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Patrizia Romualdi.

Additional information

Rosalia Cannarsa and Donatella Carretta equally contributed to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cannarsa, R., Carretta, D., Lattanzio, F. et al. ∆9-Tetrahydrocannabinol Decreases NOP Receptor Density and mRNA Levels in Human SH-SY5Y Cells. J Mol Neurosci 46, 285–292 (2012). https://doi.org/10.1007/s12031-011-9552-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-011-9552-0

Keywords

Search

Navigation