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Titolo:
SCHIZOPHRENIA IS ASSOCIATED WITH ELEVATED AMPHETAMINE-INDUCED SYNAPTIC DOPAMINE CONCENTRATIONS - EVIDENCE FROM A NOVEL POSITRON EMISSION TOMOGRAPHY METHOD
Autore:
BREIER A; SU TP; SAUNDERS R; CARSON RE; KOLACHANA BS; DEBARTOLOMEIS A; WEINBERGER DR; WEISENFELD N; MALHOTRA AK; ECKELMAN WC; PICKAR D;
Indirizzi:
NIMH,EXPT THERAPEUT BRANCH,NIH BETHESDA MD 20892 NIMH,CLIN BRAIN DISORDERS BRANCH,NIH BETHESDA MD 20892 NIH,CTR CLIN,POSITRON EMISS TOMOG DEPT BETHESDA MD 20892
Titolo Testata:
Proceedings of the National Academy of Sciences of the United Statesof America
fascicolo: 6, volume: 94, anno: 1997,
pagine: 2569 - 2574
SICI:
0027-8424(1997)94:6<2569:SIAWEA>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
IN-VIVO MICRODIALYSIS; HUMAN-BRAIN; C-11 RACLOPRIDE; KINETIC-PROPERTIES; NONHUMAN-PRIMATES; RECEPTOR-BINDING; H-3 RACLOPRIDE; RHESUS-MONKEY; INVIVO; RELEASE;
Keywords:
RACLOPRIDE; BRAIN IMAGING; STRIATUM; IN VIVO MICRODIALYSIS; PSYCHOSTIMULANTS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
47
Recensione:
Indirizzi per estratti:
Citazione:
A. Breier et al., "SCHIZOPHRENIA IS ASSOCIATED WITH ELEVATED AMPHETAMINE-INDUCED SYNAPTIC DOPAMINE CONCENTRATIONS - EVIDENCE FROM A NOVEL POSITRON EMISSION TOMOGRAPHY METHOD", Proceedings of the National Academy of Sciences of the United Statesof America, 94(6), 1997, pp. 2569-2574

Abstract

A major line of evidence that supports the hypothesis of dopamine overactivity in schizophrenia is the psychomimetic potential of agents such as amphetamine that stimulate dopamine outflow, A novel brain imaging method provides an indirect measure of in vivo synaptic dopamine concentration by quantifying the change in dopamine receptor radiotracerbinding produced by agents that alter dopamine release but do not themselves bind to dopamine receptors, The purpose of this investigation is (i) to determine the sensitivity (i.e., amount of dopamine reflected in radiotracer binding changes) of this method by examining the relationship between amphetamine-induced changes in simultaneously derivedstriatal extracellular dopamine levels with in vivo microdialysis andstriatal binding levels with the dopamine D-2/D-3 positron-emission tomography radioligand [C-11]raclopride in nonhuman primates, and (ii) to test the hypothesis of elevated amphetamine-induced synaptic dopamine levels in schizophrenia, In the nonhuman primate study (n = 4), doubling the amphetamine dose produced a doubling in [C-11] raclopride specific binding reductions, In addition, the ratio of percent mean dopamine increase to percent mean striatal binding reduction for amphetamine (0.2 mg/kg) was 44:1, demonstrating that relatively small binding changes reflect large changes in dopamine outflow, In the clinical study, patients with schizophrenia (n = 11) compared with healthy volunteers (n = 12) had significantly greater amphetamine-related reductions in [C-11]raclopride specific binding (mean +/- SEM): -22.3% (+/- 2.7) vs, -15.5% (+/- 1.8), P = 0.04, respectively, Inferences from the preclinical study suggest that the patients' elevation in synaptic dopamineconcentrations was substantially greater than controls, These data provide direct evidence for the hypothesis of elevated amphetamine-induced synaptic dopamine concentrations in schizophrenia.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/04/20 alle ore 02:40:10