Orexin A Expression and Promoter Methylation in Patients with Cannabis Dependence in Comparison to Nicotine-Dependent Cigarette Smokers and NonsmokersRotter A. · Bayerlein K. · Hansbauer M. · Weiland J. · Sperling W. · Kornhuber J. · Biermann T.
Department of Psychiatry and Psychotherapy, Friedrich Alexander University, Erlangen-Nuremberg, Germany
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Article / Publication Details
Background: The orexins (hypocretins) are neuropeptides with an origin in the lateral hypothalamus. They have been found to be crucial within the context of drug craving, withdrawal und relapse. Methods: Therefore, orexin A gene expression and promoter methylation in peripheral blood cells of 77 subjects [36 with tetrahydrocannabinol (THC) dependence, 20 nicotine-dependent cigarette smokers and 21 nonsmokers] were assessed by quantitative real-time PCR and methylation-specific digestion PCR. Results: There was a statistically significant difference in orexin A expression between the three groups [p = 0.000, F = 131.4, d.f. = 2, analysis of variance (ANOVA)]. Orexin A gene expression was statistically significantly correlated with the Satisfaction with Life Scale (r = –0.28, p = 0.018), a visual analogue scale of craving (r = 0.734, p = 0.000) and three subscales of the World Health Organization Alcohol, Smoking and Substance Involvement Screening Test, i.e. nicotine consumption (r = 0.388, p = 0.001), alcohol consumption (r = 0.354, p = 0.002) and cannabis consumption (r = 0.783, p = 0.000). The mean promoter methylation (as a percentage) was not statistically related to orexin gene expression. However, there was a statistically significant difference in promoter methylation with regard to body mass index in general (F = 2.37, d.f. = 54, p = 0.016, ANOVA). Conclusions: Orexin might be a possible target in THC as well as nicotine dependence, taking into account the effect of THC on energy homeostasis in the circuit of reward and motivation and its impact on appetite and body weight.
© 2012 S. Karger AG, Basel
- Hall W, Degenhardt L: Adverse health effects of non-medical cannabis use. Lancet 2009;374:1383–1391.
- Green B, Kavanagh D, Young R: Being stoned: a review of self-reported cannabis effects. Drug Alcohol Rev 2003;22:453–460.
- Compton WM, Grant BF, Colliver JD, Glantz MD, Stinson FS: Prevalence of marijuana use disorders in the United States: 1991–1992 and 2001–2002. JAMA 2004;291:2114–2121.
Haney M: The marijuana withdrawal syndrome: diagnosis and treatment. Curr Psychiatry Rep 2005;7:360–366.
- Stephens RS, Roffman RA, Curtin L: Comparison of extended versus brief treatments for marijuana use. J Consult Clin Psychol 2000;68:898–908.
Dani JA, Balfour DJ: Historical and current perspective on tobacco use and nicotine addiction. Trends Neurosci 2011, E-pub ahead of print.
- Felder CC, Glass M: Cannabinoid receptors and their endogenous agonists. Annu Rev Pharmacol Toxicol 1998;38:179–200.
- Howlett AC, Breivogel CS, Childers SR, Deadwyler SA, Hampson RE, Porrino LJ: Cannabinoid physiology and pharmacology: 30 years of progress. Neuropharmacology 2004;47(suppl 1):345–358.
- Cabral GA, Griffin-Thomas L: Cannabinoids as therapeutic agents for ablating neuroinflammatory disease. Endocr Metab Immune Disord Drug Targets 2008;8:159–172.
- Gong JP, Onaivi ES, Ishiguro H, Liu QR, Tagliaferro PA, Brusco A, Uhl GR: Cannabinoid CB2 receptors: immunohistochemical localization in rat brain. Brain Res 2006;1071:10–23.
- Abel EL: Cannabis: effects on hunger and thirst. Behav Biol 1975;15:255–281.
- Crespo I, Gomez de Heras R, Rodriguez de Fonseca F, Navarro M: Pretreatment with subeffective doses of Rimonabant attenuates orexigenic actions of orexin A-hypocretin 1. Neuropharmacology 2008;54:219–225.
- Bayerlein K, Kraus T, Leinonen I, Pilniok D, Rotter A, Hofner B, Schwitulla J, Sperling W, Kornhuber J, Biermann T: Orexin A expression and promoter methylation in patients with alcohol dependence comparing acute and protracted withdrawal. Alcohol 2011;45:541–547.
- Tsujino N, Sakurai T: Orexin/hypocretin: a neuropeptide at the interface of sleep, energy homeostasis, and reward system. Pharmacol Rev 2009;61:162–176.
- Hilairet S, Bouaboula M, Carriere D, Le Fur G, Casellas P: Hypersensitization of the orexin 1 receptor by the CB1 receptor: evidence for cross-talk blocked by the specific CB1 antagonist, SR141716. J Biol Chem 2003;278:23731–23737.
- Nishino S, Ripley B, Overeem S, Lammers GJ, Mignot E: Hypocretin (orexin) deficiency in human narcolepsy. Lancet 2000;355:39–40.
- Sutcliffe JG, de Lecea L: The hypocretins: setting the arousal threshold. Nat Rev Neurosci 2002;3:339–349.
- von der Goltz C, Koopmann A, Dinter C, Richter A, Rockenbach C, Grosshans M, Nakovics H, Wiedemann K, Mann K, Winterer G, Kiefer F: Orexin and leptin are associated with nicotine craving: a link between smoking, appetite and reward. Psychoneuroendocrinology 2010;35:570–577.
- Mahler SV, Smith KS, Berridge KC: Endocannabinoid hedonic hotspot for sensory pleasure: anandamide in nucleus accumbens shell enhances ‘liking’ of a sweet reward. Neuropsychopharmacology 2007;32:2267–2278.
- Harkany T, Hartig W, Berghuis P, Dobszay MB, Zilberter Y, Edwards RH, Mackie K, Ernfors P: Complementary distribution of type 1 cannabinoid receptors and vesicular glutamate transporter 3 in basal forebrain suggests input-specific retrograde signalling by cholinergic neurons. Eur J Neurosci 2003;18:1979–1992.
- Good CH, Lupica CR: Afferent-specific AMPA receptor subunit composition and regulation of synaptic plasticity in midbrain dopamine neurons by abused drugs. J Neurosci 2010;30:7900–7909.
- Palmiter RD: Is dopamine a physiologically relevant mediator of feeding behavior? Trends Neurosci 2007;30:375–381.
- Harris GC, Wimmer M, Aston-Jones G: A role for lateral hypothalamic orexin neurons in reward seeking. Nature 2005;437:556–559.
- Plaza-Zabala A, Flores A, Maldonado R, Berrendero F: Hypocretin/orexin signaling in the hypothalamic paraventricular nucleus is essential for the expression of nicotine withdrawal. Biol Psychiatry 2012;71:214–223.
- Thornton LK, Baker AL, Lewin TJ, Kay-Lambkin FJ, Kavanagh D, Richmond R, Kelly B, Johnson MP: Reasons for substance use among people with mental disorders. Addict Behav 2012;37:427–434.
- Agrawal A, Lynskey MT: Candidate genes for cannabis use disorders: findings, challenges and directions. Addiction 2009;104:518–532.
- Henquet C, Di Forti M, Morrison P, Kuepper R, Murray RM: Gene-environment interplay between cannabis and psychosis. Schizophr Bull 2008;34:1111–1121.
Ehrlich S, Walton E, Roffman JL, Weiss D, Puls I, Doehler N, Burghardt R, Lehmkuhl U, Hillemacher T, Muschler M, Frieling H: Smoking, but not malnutrition, influences promoter-specific DNA methylation of the proopiomelanocortin gene in patients with and without anorexia nervosa. Can J Psychiatry 2012;57:168–176.
- Derogatis LR, Rickels K, Rock AF: The SCL-90 and the MMPI: a step in the validation of a new self-report scale. Br J Psychiatry 1976;128:280–289.
- Diener E, Emmons RA, Larsen RJ, Griffin S: The Satisfaction With Life Scale. J Pers Assess 1985;49:71–75.
- WHO ASSIST Working Group: The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST): development, reliability and feasibility. Addiction 2002;97:1183–1194.
- Bleich S, Carl M, Bayerlein K, Reulbach U, Biermann T, Hillemacher T, Bonsch D, Kornhuber J: Evidence of increased homocysteine levels in alcoholism: the Franconian alcoholism research studies (FARS). Alcohol Clin Exp Res 2005;29:334–336.
- Bleich S, Lenz B, Ziegenbein M, Beutler S, Frieling H, Kornhuber J, Bonsch D: Epigenetic DNA hypermethylation of the HERP gene promoter induces down-regulation of its mRNA expression in patients with alcohol dependence. Alcohol Clin Exp Res 2006;30:587–591.
- Di Marzo V, Matias I: Endocannabinoid control of food intake and energy balance. Nat Neurosci 2005;8:585–589.
- Hervieu GJ, Cluderay JE, Harrison DC, Roberts JC, Leslie RA: Gene expression and protein distribution of the orexin-1 receptor in the rat brain and spinal cord. Neuroscience 2001;103:777–797.
- Valenti M, Cottone E, Martinez R, De Pedro N, Rubio M, Viveros MP, Franzoni MF, Delgado MJ, Di Marzo V: The endocannabinoid system in the brain of Carassius auratus and its possible role in the control of food intake. J Neurochem 2005;95:662–672.
- Huang H, Acuna-Goycolea C, Li Y, Cheng HM, Obrietan K, van den Pol AN: Cannabinoids excite hypothalamic melanin-concentrating hormone but inhibit hypocretin/orexin neurons: implications for cannabinoid actions on food intake and cognitive arousal. J Neurosci 2007;27:4870–4881.
- Fernandez-Espejo E, Viveros MP, Nunez L, Ellenbroek BA, Rodriguez de Fonseca F: Role of cannabis and endocannabinoids in the genesis of schizophrenia. Psychopharmacology (Berl) 2009;206:531–549.
- Lawrence AJ: Regulation of alcohol-seeking by orexin (hypocretin) neurons. Brain Res 2010;1314:124–129.
- Kalra SP, Kalra PS: Overlapping and interactive pathways regulating appetite and craving. J Addict Dis 2004;23:5–21.
- Quarta D, Valerio E, Hutcheson DM, Hedou G, Heidbreder C: The orexin-1 receptor antagonist SB-334867 reduces amphetamine-evoked dopamine outflow in the shell of the nucleus accumbens and decreases the expression of amphetamine sensitization. Neurochem Int 2010;56:11–15.
- Mamelak M: Narcolepsy and depression and the neurobiology of gammahydroxybutyrate. Prog Neurobiol 2009;89:193–219.
Thornton LK, Baker AL, Johnson MP, Lewin TJ: Attitudes and perceptions towards substances among people with mental disorders: a systematic review. Acta Psychiatr Scand 2012, E-pub ahead of print.
Zhu LY, Summah H, Jiang HN, Qu JM: Plasma orexin-A levels in COPD patients with hypercapnic respiratory failure. Mediators Inflamm 2011;2011:754847.
- Yagi S, Hirabayashi K, Sato S, Li W, Takahashi Y, Hirakawa T, Wu G, Hattori N, Ohgane J, Tanaka S, Liu XS, Shiota K: DNA methylation profile of tissue-dependent and differentially methylated regions (T-DMRs) in mouse promoter regions demonstrating tissue-specific gene expression. Genome Res 2008;18:1969–1978.
- Rotter A, Asemann R, Decker A, Kornhuber J, Biermann T: Orexin expression and promoter-methylation in peripheral blood of patients suffering from major depressive disorder. J Affect Disord 2011;131:186–192.
- Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI: Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 1990;346:561–564.
- Manzanares J, Uriguen L, Rubio G, Palomo T: Role of endocannabinoid system in mental diseases. Neurotox Res 2004;6:213–224.
Kasteridis P, Yen ST: Smoking cessation and body weight: evidence from the Behavioral Risk Factor Surveillance Survey. Health Serv Res 2012, E-pub ahead of print.
- Kastin AJ, Akerstrom V: Orexin A but not orexin B rapidly enters brain from blood by simple diffusion. J Pharmacol Exp Ther 1999;289:219–223.
- McGowan PO, Sasaki A, Huang TC, Unterberger A, Suderman M, Ernst C, Meaney MJ, Turecki G, Szyf M: Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain. PLoS One 2008;3:e2085.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.