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Titolo:
Imaging synaptic neurotransmission with in vivo binding competition techniques: A critical review
Autore:
Laruelle, M;
Indirizzi:
Columbia Univ, New York State Psychiat Inst, Dept Psychiat, New York, NY 10032 USA Columbia Univ New York NY USA 10032 Dept Psychiat, New York, NY 10032 USA Columbia Univ, Coll Phys & Surg, Dept Psychiat & Radiol, New York, NY USA Columbia Univ New York NY USA , Dept Psychiat & Radiol, New York, NY USA
Titolo Testata:
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
fascicolo: 3, volume: 20, anno: 2000,
pagine: 423 - 451
SICI:
0271-678X(200003)20:3<423:ISNWIV>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON-EMISSION-TOMOGRAPHY; DOPAMINE D-2 RECEPTORS; C-11 RACLOPRIDE BINDING; NAIVE SCHIZOPHRENIC-PATIENTS; MUSCARINIC CHOLINERGIC RECEPTOR; RHESUS-MONKEY BRAIN; NEURONS IN-VIVO; ENDOGENOUS DOPAMINE; HIGH-AFFINITY; RAT STRIATUM;
Keywords:
positron emission tomography; single-photon emission computed tomography dopamine; raclopride; IBZM; spiperone; internalization;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
215
Recensione:
Indirizzi per estratti:
Indirizzo: Laruelle, M Columbia Univ, New York State Psychiat Inst, Dept Psychiat, 1051 RiversideDr,Unit 42, New York, NY 10032 USA Columbia Univ 1051 RiversideDr,Unit 42 New York NY USA 10032
Citazione:
M. Laruelle, "Imaging synaptic neurotransmission with in vivo binding competition techniques: A critical review", J CEREBR B, 20(3), 2000, pp. 423-451

Abstract

Several groups have provided evidence that positron emission tomography (PET) and single-photon emission computed tomography (SPECT) neuroreceptor imaging techniques might be applied to measure acute fluctuations in dopamine(DA) synaptic concentration in the living human brain. Competition betweenDA and radioligands for binding to D-2 receptor is the principle underlying this approach. This new application of neuroreceptor imaging provides a dynamic measurement of neurotransmission that is likely to be informative toour understanding of neuropsychiatric conditions. This article reviews anddiscusses the body of data supporting the feasibility and potential of this imaging paradigm. Endogenous competition studies performed in rodents, nonhuman primates, and humans are first summarized. After this overview, the validity of the model underlying the interpretation of these imaging data is critically assessed. The current reference model is defined as the occupancy model, since changes in radiotracer binding potential (BP) are assumed to be directly caused by changes in occupancy of D-2 receptors by DA. Experimental data supporting this model are presented. The evidence that manipulation of DA synaptic levels induces change in the BP of several D2 radiotracers (catecholamines and benzamides) is unequivocal. The fact that these changes in BP are mediated by changes in DA synaptic concentration is well documented. The relationship between the magnitude of BP changes measured with PET or SPECT and the magnitude of changes in DA concentration measured bymicrodialysis supports the use of these noninvasive techniques to measure changes in neurotransmission. On the other hand, several observations remain unexplained. First, the amphetamine-induced changes in the BP of D-2 receptor antagonists [I-123]IBZM and [C-11]raclopride last longer than amphetamine-induced changes in DA extracellular concentration. Second, nonbenzamideD-2 receptor antagonists, such as spiperone and pimozide, are not affectedby changes in DA release, or are affected in a direction opposite to that predicted by the occupancy model. Similar observations are reported with D-1 radiotracers. These results suggest that the changes in BP following changes in DA concentration might not be fully accounted by a simple occupancy model. Specifically, the data are reviewed supporting that agonist-mediatedreceptor internalization might play an important role in characterizing receptor-ligand interactions. Finally, it is proposed that a better understanding of the mechanism underlying the effects observed with benzamides is essential to develop this imaging technique to other receptor systems.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 18:34:00