Imaging VS Postmortem Receptor Studies: What You See is What You Get?
Postmortem research historically provided the technical and evidential basis for in vivo receptor imaging. In vitro mapping of receptor distribution and density is an essential first step for novel tracer development in order to image brain receptors in a living human subject. The chapter reviews the technical distinctions between receptor estimation postmortem and in vivo. The advantages and disadvantages of each approach are also discussed with respect to psychiatric disorder in particular. The neuropharmacology of schizophrenia has been most studied with neuroreceptor imaging and is used as an instructive example of the contribution of both methodologies to understanding the role of dopamine in the disorder. These data include simple studies estimating dopamine D2 receptors in schizophrenia, dynamic in vivo challenges of the dopamine system, and examining the links between dopamine D2 receptor occupancy by antipsychotic drugs and their toxic and therapeutic effects. These studies reveal the necessity of bridging the gap between ante- and postmortem research in schizophrenia and other disorders.
KeywordsAntipsychotic Drug Receptor Occupancy Striatal Dopamine Atypical Antipsychotic Drug Bioi Psychiatry
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- Benes FM. (2001) The study of neural circuitry in schizophrenia using postmortem and brain imaging approaches. Biol Psychiatry 2001; 49: 3S.Google Scholar
- Bigliani V, Mulligan RS, Acton PD, Ohlsen RI, Pike VW, Ell PJ, Gacinovic S, Kerwin RW, Pilowsky LS. Striatal and temporal cortical D2/D3 receptor occupancy by olanzapine-a 1231 epidepride single photon emission tomography (SPET) study. Psychopharmacology 2000; 150: 132–140.PubMedCrossRefGoogle Scholar
- Clow A, Theodoru A, Jenner P, et al. Changes in rat striatal dopamine turnover and receptor activity during one year’s neuroleptic administration. Eur J Pharmacology 1980; 63: 135144.Google Scholar
- Ichise M, Meyer J, Yonekura Y. An introduction to PET and SPECT neuroreceptor quantification models. J Nuc Med 2001; 42: 755–763.Google Scholar
- Janowsky A, Neve KA, Kinsie MJ, Taylor B, de Paulis T, Belknap J. Extrastriatal dopamine D2 receptors: distribution, pharmacological characterisation and region specific regulation by clozapine. J Pharm Exp Ther 1992; 261: 1282–1290.Google Scholar
- Kapur S, Barlow K, Vanderspek SC, Javanmard M, Nobrega JN. Drug induced receptor occupancy: substantial differences in measurements made in vivo vs ex vivo. Psychophannacology 2001; published online DOI 10.1007/x002130100790.Google Scholar
- Laruelle M, Abi-Dargham A, van Dyck CH, Gil R, D’Souza CD, Erdos J, McCance E, Rosenblatt W, Fingado C, Zoghbi SS, Baldwin RM, Seibyl JP, Krystal JH, Charney DS, Innis RB. Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proc Natl Acad Sci U S A 1996; 93: 9235–40.PubMedCrossRefGoogle Scholar
- Lamelle M. Imaging synaptic neurotransmission with in vivo binding competition techniques-a criticial review, J Cer Blood Flow Metab 2000; 20: 423–451.Google Scholar
- Lee T, Seeman P (1980) Elevation of Brain Neuroleptic/Dopamine receptors in Schizophrenia, Am J Psychiary 1980; 137: 191–197.Google Scholar
- Mackay AVP, Iversen LL, Rossor M, Spokes E, Bird E, Arregui A, Creese I, Snyder SH. Increased brain dopamine and dopamine receptors in schizophrenia Arch Gen Psychiat 1982; 39: 991–997.Google Scholar
- Mann JJ. Postmortem versus in vivo imaging: comparison of anatomical and temporal scale. Biol Psychiatry 2001; 49: 2S.Google Scholar
- Moore H, West AR, Grace AA. The regulation of forebrain dopamine transmission: relevance to the pathophysiology and psychopathology of schizophrenia Biol Psychiatry 1999; 46: 40–55.Google Scholar
- Nyberg S, Farde L, Eriksson L, Halldin C, Eriksson B. 5HT2 and D2 dopamine receptor occupancy by risperidone in the living human brain. Psychopharmacology 1993; 110: 265272.Google Scholar
- Pilowsky LS, Costa DC, Ell PJ, Murray R, Verhoeff N, Kerwin RW. Clozapine, single photon emission tomography and the D2 dopamine receptor blockade hypothesis of schizophrenia Lancet 1992; 340: 199–202.Google Scholar
- Pilowsky LS, Costa DC, Ell PJ, Verhoeff NPLG, Murray RM, Kerwin RW. D2 dopamine receptor binding in the basal ganglia of antipsychotic free schizophrenic patients-a 1231 IBZM single photon emission tomography (SPET) study. Br J Psychiatry 1994; 164: 16–26.Google Scholar
- Silvestri S, Seeman MV, Negrete JC, Houle S, Shammi CM, Remington GJ, Kapur S, Zipursky RB, Wilson AA, Christensen BK, Seeman P. Increased dopamine D2 receptor binding after long-term treatment with antipsychotics in humans: a clinical PET study. Psychopharmacology (Berl) 2000; 152: 174–80.CrossRefGoogle Scholar
- Travis MJ, Busatto GF, Pilowsky LS, Mulligan R, Acton PD, Gacinovic S, Mertens J, Terriere D, Costa DC, Ell PJ, Kerwin RW. 5-HT2A receptor blockade in patients with schizophrenia treated with risperidone or clozapine. A SPET study using the novel 5HT2A ligand 123I-5-I-R-91150. Br J Psychiatry 1998; 173: 236–41.PubMedCrossRefGoogle Scholar