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Logo of neuroscibullNeuroscience Bulletin
 
Neurosci Bull. 2007 November; 23(6): 341–347.
Published online 2008 February 3. doi:  10.1007/s12264-007-0051-9
PMCID: PMC5550648

Language: English | Chinese

No changes in densities of cannabinoid receptors in the superior temporal gyrus in schizophrenia

精神分裂症患者颞上回的大麻素受体密度没有显著性变化

Abstract

Objective

In recent years, abnormal changes in the endocannabinoid system have been found in schizophrenia. The superior temporal gyrus (STG) is strongly implicated in the pathophysiology of schizophrenia, particularly with regards to auditory hallucinations. In this study, we investigated the binding density of cannabinoid CB1 receptors in the STG of schizophrenia patients compared to control subjects.

Methods

Quantitative autoradiography was used to investigate the binding densities of [3H]SR141716A (a selective antagonist) and [3H]CP-55940 (an agonist) to the CB1 receptors in the STG. Post-mortem brain tissue was obtained from the NSW Tissue Resource Centre (Australia).

Results

Contrasting to previous findings in the alterations of CB1 receptor densities in the prefrontal, anterior and posterior cingulate cortex of schizophrenia, which were suggested to be associated to impairment of cognition function, no significant difference was found between the schizophrenia and control cases in both [3H]SR141716A and [3H]CP-55940 binding.

Conclusion

We suggest that CB1 receptors in the STG are not involved in the pathology of schizophrenia and the auditory hallucination symptom of this disease.

Keywords: schizophrenia, cannabinoid receptor, autoradiography, superior temporal gyrus

摘要

目的

近年来研究发现, 在精神分裂症患者的内源性大麻素递质系统会出现异常变化, 而颞上回在精神分裂症的病理生理机制中和幻听症状密切相关。 因此, 对照正常人群, 我们研究了精神分裂症患者颞上回大麻素CB-1受体的密度变化。

方法

采用定量放射自显影技术, 通过[3H]SR141716A(CB-1受体选择性拮抗剂)和 [3H]CP-55940(CB-1受体激动剂)检测颞上回CB-1受体密度水平。 死后脑组织由澳大利亚新南威尔士州组织资源中心提供。

结果

先前研究发现, 精神分裂症患者与认知功能失常相关的额前叶, 前、 后扣带回皮质的CB-1 受体密度水平有异常改变. 与此相反, 本研究发现在精神分裂症患者的由[3H]SR141716A和[3H]CP-55940检测的颞上回大麻素受体密度水平和对照组比较没有显著变化。

结论

我们认为颞上回大麻素CB-1受体和精神分裂症患者的发病及幻听症状无关。

关键词: 精神分裂症, 大麻素受体, 放射自显影技术, 颞上回

References

[1] Degenhardt L., Hall W. Cannabis and psychosis. Curr Psychiat Rep. 2002;4:191–196. doi: 10.1007/s11920-002-0026-5. [PubMed] [Cross Ref]
[2] Skosnik P.D., Spatz-Glenn L., Park S. Cannabis use is associated with schizotypy and attentional disinhibition. Schizophr Res. 2001;48:83–92. doi: 10.1016/S0920-9964(00)00132-8. [PubMed] [Cross Ref]
[3] Huestis M.A., Gorelick D.A., Heishman S.J., Preston K.L., Nelson R.A., Moolchan E.T., et al. Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716. Arch Gen Psychiat. 2001;58:322–328. doi: 10.1001/archpsyc.58.4.322. [PubMed] [Cross Ref]
[4] Johns A. Psychiatric effects of cannabis. Brit J Psychiat. 2001;178:116–122. doi: 10.1192/bjp.178.2.116. [PubMed] [Cross Ref]
[5] Devane W.A., Hanus L., Breuer A., Pertwee R.G., Stevenson L.A., Griffin G., et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. 1992;258:1946–1949. doi: 10.1126/science.1470919. [PubMed] [Cross Ref]
[6] Di Marzo V., Fontana A., Cadas H., Schinelli S., Cimino G., Schwartz J.C., et al. Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature. 1994;372:686–691. doi: 10.1038/372686a0. [PubMed] [Cross Ref]
[7] Emrich H.M., Leweke F.M., Schneider U. Towards a cannabinoid hypothesis of schizophrenia: cognitive impairments due to dysregulation of the endogenous cannabinoid system. Pharmacol Biochem Behav. 1997;56:803–807. doi: 10.1016/S0091-3057(96)00426-1. [PubMed] [Cross Ref]
[8] Ujike H., Morita Y. New perspectives in the studies on endocannabinoid and cannabis: cannabinoid receptors and schizophrenia. J Pharmacol Sci. 2004;96:376–381. doi: 10.1254/jphs.FMJ04003X4. [PubMed] [Cross Ref]
[9] Leweke F.M., Giuffrida A., Wurster U., Emrich H.M., Piomelli D. Elevated endogenous cannabinoids in schizophrenia. Neuroreport. 1999;10:1665–1669. doi: 10.1097/00001756-199906030-00008. [PubMed] [Cross Ref]
[10] Giuffrida A., Leweke F.M., Gerth C.W., Schreiber D., Koethe D., Faulhaber J., Klosterkotter J., Piomelli D. Cerebrospinal anandamide levels are elevated in acute schizophrenia and are inversely correlated with psychotic symptoms. Neuropsychopharmacology. 2004;29:2108–2114. doi: 10.1038/sj.npp.1300558. [PubMed] [Cross Ref]
[11] Dean B., Sundram S., Bradbury R., Scarr E., Copolov D. Studies 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 use. Neuroscience. 2001;103:9–15. doi: 10.1016/S0306-4522(00)00552-2. [PubMed] [Cross Ref]
[12] Zavitsanou K., Garrick T., Huang X.F. Selective antagonist [3H] SR141716A binding to cannabinoid CB1 receptors is increased in the anterior cingulate cortex in schizophrenia. Prog Neuro-Psychopharmacol Biol Psychiat. 2004;28:355–360. doi: 10.1016/j.pnpbp.2003.11.005. [PubMed] [Cross Ref]
[13] Newell K.A., Deng C., Huang X.F. Increased cannabinoid receptor density in the posterior cingulate cortex in schizophrenia. Exp Brain Res. 2006;172:556–560. doi: 10.1007/s00221-006-0503-x. [PubMed] [Cross Ref]
[14] Kim J.J., Crespo-Facorro B., Andreasen N.C., O’Leary D.S., Magnotta V., Nopoulos P. Morphology of the lateral superior temporal gyrus in neuroleptic naive patients with schizophrenia: relationship to symptoms. Schizophr Res. 2003;60:173–181. [PubMed]
[15] Glass M., Dragunow M., Faull R.L. Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neuroscience. 1997;77:299–318. doi: 10.1016/S0306-4522(96)00428-9. [PubMed] [Cross Ref]
[16] Jablensky A., Hugler H., Von Cranach M., Kalinov K. Kraepelin revisited: a reassessment and statistical analysis of dementia praecox and manic-depressive insanity in 1908. Psychol Med. 1993;23:843–858. doi: 10.1017/S0033291700026337. [PubMed] [Cross Ref]
[17] Keks N., Hill C., Opeskin K., Copolov D., Dean B. Psychiatric diagnosis after death: the problems of accurate diagnosis. In: Dean B., Hyde T.M., Kleinman J., editors. The Use of CNS Autopsy Tissue in Psychiatric Research: A Practical Guide. Sydney: Gordon & Breach Science Publishers; 1988. pp. 19–37.
[18] Newell K.A., Zavitsanou K., Jew S.K., Huang X.F. Alterations of muscarinic and GABA receptor binding in the posterior cingulate cortex in schizophrenia. Prog Neuro psychopharmacol Biol Psychiatry. 2007;31:225–233. doi: 10.1016/j.pnpbp.2006.07.004. [PubMed] [Cross Ref]
[19] Oviedo A., Glowa J., Herkenham M. Chronic cannabinoid administration alters cannabinoid receptor binding in rat brain: a quantitative autoradiographic study. Brain Res. 1993;616:293–302. doi: 10.1016/0006-8993(93)90220-H. [PubMed] [Cross Ref]
[20] Rodriguez de Fonseca F., Gorriti M.A., Fernandez-Ruiz J.J., Palomo T., Ramos J.A. Downregulation of rat brain cannabinoid binding sites after chronic delta 9-tetrahydrocannabinol treatment. Pharmacol Biochem Behav. 1994;47:33–40. doi: 10.1016/0091-3057(94)90108-2. [PubMed] [Cross Ref]
[21] Sundram S., Copolov D., Dean B. Clozapine decreases [3H] CP55940 binding to the cannabinoid 1 receptor in the rat nucleus accumbens. Naunyn-Schmiedebergs Arch Pharmacol. 2005;371:428–433. doi: 10.1007/s00210-005-1074-2. [PubMed] [Cross Ref]
[22] Gaser C., Nenadic I., Volz H.P., Buchel C., Sauer H. Neuroanatomy of “hearing voices”: a frontotemporal brain structural abnormality associated with auditory hallucinations in schizophrenia. Cereb Cortex. 2004;14:91–96. doi: 10.1093/cercor/bhg107. [PubMed] [Cross Ref]
[23] Silbersweig D.A., Stern E., Frith C., Cahill C., Holmes A., Grootoonk S., Seaward J., McKenna P., Chua S.E., Schnorr L., Johnes T., Frackowiak R.S.J. A functional neuroanatomy of hallucination in schizophrenia. Nature. 1995;378:176–179. doi: 10.1038/378176a0. [PubMed] [Cross Ref]
[24] Lennox B.R., Park S.B., Medley I., Morris P.G., Jones P.B. The functional anatomy of auditory hallucinations in schizophrenia. Psychiat Res. 2000;100:13–20. doi: 10.1016/S0925-4927(00)00068-8. [PubMed] [Cross Ref]
[25] Voruganti L.N., Slomka P., Zabel P., Mattar A., Awad A.G. Cannabis induced dopamine release: an in-vivo SPECT study. Psychiat Res. 2001;107:173–177. doi: 10.1016/S0925-4927(01)00104-4. [PubMed] [Cross Ref]
[26] Ameri A. The effects of cannabinoids on the brain. Prog Neurobiol. 1999;58:315–348. doi: 10.1016/S0301-0082(98)00087-2. [PubMed] [Cross Ref]
[27] Vinod K.Y., Hungund B.L. Cannabinoid-1 receptor: a novel target for the treatment of neuropsychiatric disorders. Expert Opin Ther Targets. 2006;10:203–210. doi: 10.1517/14728222.10.2.203. [PubMed] [Cross Ref]

Articles from Neuroscience Bulletin are provided here courtesy of Springer