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Expression of CB1 cannabinoid receptor in the anterior cingulate cortex in schizophrenia, bipolar disorder, and major depression

  • D. Koethe
  • I. C. Llenos
  • J. R. Dulay
  • C. Hoyer
  • E. F. Torrey
  • F. M. Leweke
  • S. Weis
Article

Summary

The human endogenous cannabinoid system is an appealing target in the investigation of psychiatric disorders. In schizophrenia, endocannabinoids and their receptors are involved in the pathology of the disease. Previous studies reported an increased radioligand binding to cannabinoid receptors 1 (CB1) in schizophrenia, both in the dorsolateral prefrontal cortex and in the anterior cingulate cortex (ACC). We analyzed the expression of the CB1 receptors in the ACC at the protein level using immunohistochemistry. In a quantitative postmortem study, 60 patients suffering from schizophrenia, bipolar disorder, major depression and controls were included. Numerical densities of neurons and glial cells immunopositive for CB1 receptors were evaluated. No evidence of an increased or decreased density of CB1 receptor immunopositive cells in schizophrenia or bipolar disorder was found. In major depression, CB1 receptor immunopositive glial cells in the grey matter were decreased. Furthermore, our data show that different medications have an impact on the expression of CB1 receptors in the ACC.

Keywords: CB1-cannabinoid receptor, schizophrenia, bipolar disorder, depression, anterior cingulate gyrus, immunohistochemistry, postmortem 

References

  1. Andersson, M, Terasmaa, A, Fuxe, K, Stromberg, I 2005Subchronic haloperidol increases CB(1) receptor binding and G protein coupling in discrete regions of the basal gangliaJ Neurosci Res82264272CrossRefPubMedGoogle Scholar
  2. Andreasson, S, Allebeck, P, Engstrom, A, Rydberg, U 1987Cannabis and schizophrenia. A longitudinal study of Swedish conscriptsLancet214831486CrossRefPubMedGoogle Scholar
  3. Arseneault, L, Cannon, M, Poulton, R, Murray, R, Caspi, A, Moffitt, TE 2002Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective studyBMJ32512121213CrossRefPubMedGoogle Scholar
  4. Baethge, C, Baldessarini, RJ, Khalsa, HM, Hennen, J, Salvatore, P, Tohen, M 2005Substance abuse in first-episode bipolar I disorder: indications for early interventionAm J Psychiatry16210081010CrossRefPubMedGoogle Scholar
  5. Benes, FM 2000Emerging principles of altered neural circuitry in schizophreniaBrain Res Brain Res Rev31251269CrossRefPubMedGoogle Scholar
  6. Cotter, D, Mackay, D, Landau, S, Kerwin, R, Everall, I 2001Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorderArch Gen Psychiatry58545553CrossRefPubMedGoogle Scholar
  7. Dean, B, Sundram, S, Bradbury, R, Scarr, E, Copolov, D 2001Studies on [3H]CP-55940 binding in the human central nervous system: regional specific changes in density of cannabinoid-1 receptors associated with schizophrenia and cannabis useNeuroscience103915CrossRefPubMedGoogle Scholar
  8. Devane, WA, Hanus, L, Breuer, A, Pertwee, RG, Stevenson, LA, Griffin, G, Gibson, D, Mandelbaum, A, Etinger, A, Mechoulam, R 1992Isolation and structure of a brain constituent that binds to the cannabinoid receptorScience25819461949CrossRefPubMedGoogle Scholar
  9. Di Marzo, V, Fontana, A, Cadas, H, Schinelli, S, Cimino, G, Schwartz, JC, Piomelli, D 1994Formation and inactivation of endogenous cannabinoid anandamide in central neuronsNature372686691CrossRefPubMedGoogle Scholar
  10. Egertova, M, Elphick, MR 2000Localisation of cannabinoid receptors in the rat brain using antibodies to the intracellular C-terminal tail of CBJ Comp Neurol422159171CrossRefPubMedGoogle Scholar
  11. Felder, CC, Veluz, JS, Williams, HL, Briley, EM, Matsuda, LA 1992Cannabinoid agonists stimulate both receptor- and non-receptor-mediated signal transduction pathways in cells transfected with and expressing cannabinoid receptor clonesMol Pharmacol42838845PubMedGoogle Scholar
  12. Giuffrida, A, Parsons, LH, Kerr, TM, de Fonseca, FR, Navarro, M, Piomelli, D 1999Dopamine activation of endogenous cannabinoid signaling in dorsal striatumNat Neurosci2358363CrossRefPubMedGoogle Scholar
  13. Giuffrida, A, Leweke, FM, Gerth, CW, Schreiber, D, Koethe, D, Faulhaber, J, Klosterkötter, J, Piomelli, D 2004Cerebrospinal anandamide levels are elevated in acute schizophrenia and are inversely correlated with psychotic symptomsNeuropsychopharmacology2921082114CrossRefPubMedGoogle Scholar
  14. Glass, M, Dragunow, M, Faull, RL 1997Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brainNeuroscience77299318CrossRefPubMedGoogle Scholar
  15. Gobbi G, Bambico FR, Mangieri R, Bortolato M, Campolongo P, Solinas M, Cassano T, Morgese MG, Debonnel G, Duranti A, Tontini A, Tarzia G, Mor M, Trezza V, Goldberg SR, Cuomo V, Piomelli D (2005) Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis. PNAS, pp 18620–18625Google Scholar
  16. Gong, JP, Onaivi, ES, Ishiguro, H, Liu, QR, Tagliaferro, PA, Brusco, A, Uhl, GR 2006Cannabinoid CB2 receptors: immunohistochemical localization in rat brainBrain Res10711023CrossRefPubMedGoogle Scholar
  17. Gundersen, HJG 1977Notes on the estimation of the numerical density of arbitrary profiles: the edge effectsJ Microscopy111219223Google Scholar
  18. Haug, H 1986History of neuromorphometryJ Neurosci Methods18117CrossRefPubMedGoogle Scholar
  19. Haug, H, Kühl, S, Mecke, E, Sass, N, Wasner, K 1984The significance of morphometric procedures in the investigation of age changes in cytoarchtectonic structures of human brainJ Hirnforsch25353374PubMedGoogle Scholar
  20. Hsieh, C, Brown, S, Derleth, C, Mackie, K 1999Internalization and recycling of the CB1 cannabinoid receptorJ Neurochem73493501CrossRefPubMedGoogle Scholar
  21. Hungund, BL, Vinod, KY, Kassir, SA, Basavarajappa, BS, Yalamanchili, R, Cooper, TB, Mann, JJ, Arango, V 2004Upregulation of CB1 receptors and agonist-stimulated [35S]GTPgammaS binding in the prefrontal cortex of depressed suicide victimsMol Psychiatry9184190CrossRefPubMedGoogle Scholar
  22. Knable, MB, Barci, BM, Bartko, JJ, Webster, MJ, Torrey, EF 2002Abnormalities of the cingulate gyrus in bipolar disorder and other severe psychiatric illnesses: postmortem findings from the Stanley Foundation Neuropathology Consortium and literature reviewClin Neurosci Res2171181CrossRefGoogle Scholar
  23. Leweke, FM, Giuffrida, A, Wurster, U, Emrich, HM, Piomelli, D 1999Elevated endogenous cannabinoids in schizophreniaNeuro Report1016651669Google Scholar
  24. Linszen, DH, Dingemans, PM, Lenior, ME 1994Cannabis abuse and the course of recent-onset schizophrenic disordersArch Gen Psychiatry51273279PubMedGoogle Scholar
  25. Newell, KA, Deng, C, Huang, XF 2006Increased cannabinoid receptor density in the posterior cingulate cortex in schizophreniaExp Brain Res172556560CrossRefPubMedGoogle Scholar
  26. Öngür, D, Drevets, WC, Price, JL 1998Glial reduction in the subgenual prefrontal cortex in mood disordersProc Natl Acad Sci USA951329013295CrossRefPubMedGoogle Scholar
  27. Pertwee, RG 1999Pharmacology of cannabinoid receptor ligandsCurr Med Chem6635664PubMedGoogle Scholar
  28. Pettit, DA, Harrison, MP, Olson, JM, Spencer, RF, Cabral, GA 1998Immunohistochemical localization of the neural cannabinoid receptor in rat brainJ Neurosci Res51391402CrossRefPubMedGoogle Scholar
  29. Piomelli, D 2003The molecular logic of endocannabinoid signallingNat Rev Neurosci4873884CrossRefPubMedGoogle Scholar
  30. Rodriguez de Fonseca, F, Gorriti, MA, Fernandez Ruiz, JJ, Palomo, T, Ramos, JA 1994Downregulation of rat brain cannabinoid binding sites after chronic delta 9-tetrahydrocannabinol treatmentPharmacol Biochem Behav473340CrossRefPubMedGoogle Scholar
  31. Sim-Selley, LJ, Schechter, NS, Rorrer, WK, Dalton, GD, Hernandez, J, Martin, BR, Selley, DE 2006Prolonged recovery rate of CB1 receptor adaptation after cessation of chronic cannabinoid administrationMol Pharmacol70986996CrossRefPubMedGoogle Scholar
  32. Sundram, S, Bradbury, R, Copolov, D, Dean, B 2000The effects of antipsychotic drug treatment on cannabinoid receptors in rat brainProc Australian Neuroscience Society, Melbourne1175Google Scholar
  33. Torrey, EF, Webster, M, Knable, M, Johnston, N, Yolken, RH 2000The Stanley Foundation Brain Collection and Neuropathology ConsortiumSchizophr Res44151155CrossRefPubMedGoogle Scholar
  34. Tsou, K, Brown, S, Sanudo-Pena, MC, Mackie, K, Walker, JM 1997Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous systemNeuroscience83393411CrossRefGoogle Scholar
  35. Tzavara, ET, Davis, RJ, Perry, KW, Li, X, Salhoff, C, Bymaster, FP, Witkin, JM, Nomikos, GG 2003The CB1 receptor antagonist SR141716A selectively increases monoaminergic neurotransmission in the medial prefrontal cortex: implications for therapeutic actionsBr J Pharmacol138544553CrossRefPubMedGoogle Scholar
  36. Van Sickle, MD, Duncan, M, Kingsley, PJ, Mouihate, A, Urbani, P, Mackie, K, Stella, N, Makriyannis, A, Piomelli, D, Davison, JS, Marnett, LJ, Di Marzo, V, Pittman, QJ, Patel, KD, Sharkey, KA 2005Identification and functional characterization of brainstem cannabinoid CB2 receptorsScience310329332CrossRefPubMedGoogle Scholar
  37. Vinod, KY, Hungund, BL 2006Cannabinoid-1 receptor: a novel target for the treatment of neuropsychiatric disordersExpert Opin Ther Targets10203210CrossRefPubMedGoogle Scholar
  38. Weis S (1991) Image processing and computer graphics. Theory and applications. OCG Schriftenr 58. Oldenbourg, München, pp 306–326Google Scholar
  39. Wilson, RI, Nicoll, RA 2002Endocannabinoid signaling in the brainScience296678682CrossRefPubMedGoogle Scholar
  40. Zavitsanou, K, Huang, XF 2002Decreased [(3)H]spiperone binding in the anterior cingulate cortex of schizophrenia patients: an autoradiographic studyNeuroscience109709716CrossRefPubMedGoogle Scholar
  41. Zavitsanou, K, Ward, PB, Huang, XF 2002Selective alterations in ionotropic glutamate receptors in the anterior cingulate cortex in schizophreniaNeuropsychopharmacology27826833CrossRefPubMedGoogle Scholar
  42. Zavitsanou, K, Garrick, T, Huang, XF 2004Selective antagonist [3H]SR141716A binding to cannabinoid CB1 receptors is increased in the anterior cingulate cortex in schizophreniaProg Neuropsychopharmacol Biol Psychiatry28355360CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • D. Koethe
    • 1
  • I. C. Llenos
    • 2
  • J. R. Dulay
    • 2
  • C. Hoyer
    • 1
  • E. F. Torrey
    • 2
  • F. M. Leweke
    • 1
  • S. Weis
    • 2
  1. 1.Department of Psychiatry and PsychotherapyUniversity of CologneCologneGermany
  2. 2.Stanley Laboratory for Brain Research and Neuropathology, Departments of Psychiatry and PathologyUniformed Services University of the Health Sciences, and The Stanley Medical Research InstituteBethesdaUSA

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